{"entity": "journal", "iuid": "1bebf40eb0634d769c68121d8dd8ff62", "timestamp": "2026-07-18T02:22:35.962Z", "links": {"self": {"href": "https://publications.scilifelab.se/journal/J.%20Clin.%20Endocrinol.%20Metab..json"}, "display": {"href": "https://publications.scilifelab.se/journal/J.%20Clin.%20Endocrinol.%20Metab."}}, "title": "J. Clin. Endocrinol. Metab.", "issn": "1945-7197", "issn-l": "0021-972X", "publications_count": 17, "publications": [{"entity": "publication", "iuid": "02b3955223f04da1b7d8470ef00171e2", "links": {"self": {"href": "https://publications.scilifelab.se/publication/02b3955223f04da1b7d8470ef00171e2.json"}, "display": {"href": "https://publications.scilifelab.se/publication/02b3955223f04da1b7d8470ef00171e2"}}, "title": "Cold-induced serum short-chain fatty acids act as markers of brown adipose tissue metabolism in humans.", "authors": [{"family": "Monfort-Pires", "given": "Milena", "initials": "M", "orcid": "0000-0002-1652-8083", "researcher": {"href": "https://publications.scilifelab.se/researcher/128d4268cabc4117bff0065b9960a648.json"}}, {"family": "U-Din", "given": "Mueez", "initials": "M"}, {"family": "de Mello", "given": "Vanessa", "initials": "V"}, {"family": "Saari", "given": "Teemu", "initials": "T", "orcid": "0000-0002-3212-6906", "researcher": {"href": "https://publications.scilifelab.se/researcher/871d414babfb4a158e5bb77f66cfbe72.json"}}, {"family": "Raiko", "given": "Juho", "initials": "J"}, {"family": "Kerminen", "given": "Edla", "initials": "E"}, {"family": "Rajander", "given": "Johan", "initials": "J"}, {"family": "Hanhineva", "given": "Kati", "initials": "K"}, {"family": "Fromme", "given": "Tobias", "initials": "T"}, {"family": "Landberg", "given": "Rikard", "initials": "R", "orcid": "0000-0002-6399-7608", "researcher": {"href": "https://publications.scilifelab.se/researcher/4472ec17986146d1a095acdb202815e6.json"}}, {"family": "Klingenspor", "given": "Martin", "initials": "M"}, {"family": "Virtanen", "given": "Kirsi A", "initials": "KA"}], "type": "journal article", "published": "2025-11-05", "journal": {"title": "J. Clin. Endocrinol. Metab.", "issn": "1945-7197", "issn-l": "0021-972X"}, "abstract": "Short-chain fatty acids (SCFAs) produced from dietary fibre fermentation can regulate adipose tissue metabolism through signalling pathways involving G-protein-coupled receptors and histone deacetylase inhibition. While preclinical studies suggest they enhance thermogenesis, their role in human brown adipose tissue (BAT) under different thermal conditions remains unclear.\n\nThis study explores the associations between circulating SCFAs and human BAT metabolism at room temperature and after cold exposure.\n\nThis cross-sectional study included data from 71 adults (20-55 years, BMI 19-44 kg/m\u00b2). Dynamic [15O]O2, [15O]H2O, [\u00b9\u2078F]FDG, and [\u00b9\u2078F]FTHA PET/CT scans were used to assess BAT metabolism. Serum SCFAs were quantified using LC-MS, and gene expression in biopsy-excised BAT samples (n=14) was analysed. Participants were stratified into low- and high-BAT groups based on [\u00b9\u2078F]FDG or [\u00b9\u2078F]FTHA uptakes.\n\nCold-induced acetate and propionate were positively associated with key in vivo BAT metabolism indicators, namely non-esterified fatty acids (NEFA) uptake and oxygen consumption. Only in the high-BAT group were circulating SCFAs maintained after cold exposure. BAT transcriptome revealed that genes involved in SCFA metabolism (such as conversion to acetyl-CoA) correlated with thermogenic and lipid metabolism genes exclusively in the high-BAT group, suggesting a distinct molecular link between SCFA pathways and BAT function.\n\nCirculating SCFAs are linked with BAT oxidative metabolism and NEFA uptake during cold exposure. The observed correlations between SCFA catabolic genes and thermogenic markers suggest that metabolically active BAT may selectively engage SCFA-related pathways, pointing to a potential mechanistic role of SCFAs in supporting BAT function in humans.", "doi": "10.1210/clinem/dgaf607", "pmid": "41206219", "labels": {"Chalmers Mass Spectrometry Infrastructure": "Collaborative"}, "xrefs": [{"db": "pii", "key": "8315282"}], "notes": [], "created": "2025-12-01T05:42:30.155Z", "modified": "2025-12-01T05:42:30.603Z"}, {"entity": "publication", "iuid": "f0fcb0e459e6426fab71064e0db96eee", "links": {"self": {"href": "https://publications.scilifelab.se/publication/f0fcb0e459e6426fab71064e0db96eee.json"}, "display": {"href": "https://publications.scilifelab.se/publication/f0fcb0e459e6426fab71064e0db96eee"}}, "title": "Parathyroidectomy Restores Muscle Strength and Transcriptome in Individuals with Primary Hyperparathyroidism.", "authors": [{"family": "Bj\u00f6rnsdotter-\u00d6berg", "given": "Sofia", "initials": "S"}, {"family": "Koman", "given": "Anna", "initials": "A", "orcid": "0000-0003-3196-7057", "researcher": {"href": "https://publications.scilifelab.se/researcher/518d3806b27d4b19822b8572b90f36a5.json"}}, {"family": "Skorpil", "given": "Mikael", "initials": "M"}, {"family": "Ryd\u00e9n", "given": "Henric", "initials": "H"}, {"family": "Lanner", "given": "Johanna T", "initials": "JT"}, {"family": "Krook", "given": "Anna", "initials": "A"}, {"family": "Nilsson", "given": "Inga-Lena", "initials": "IL"}, {"family": "Pillon", "given": "Nicolas J", "initials": "NJ"}, {"family": "Nyl\u00e9n", "given": "Carolina", "initials": "C", "orcid": "0000-0002-8445-7221", "researcher": {"href": "https://publications.scilifelab.se/researcher/2fb57024f0b2492988a3dbad9fafe198.json"}}], "type": "journal article", "published": "2025-07-21", "journal": {"title": "J. Clin. Endocrinol. Metab.", "issn": "1945-7197", "issn-l": "0021-972X"}, "abstract": "Primary hyperparathyroidism leads to hypercalcemia and muscle dysfunction. Muscle weakness is associated with increased morbidity and mortality but is overlooked in surgical treatment guidelines. While parathyroidectomy is the only curative treatment, its effects on skeletal muscle strength and molecular remodelling remain underexplored.\n\nDetermining functional and molecular changes in skeletal muscle before and after parathyroidectomy.\n\nA prospective observational study was conducted in the spring and fall of 2023.\n\nPatients underwent surgery at the Endocrine and Sarcoma section at the Karolinska University Hospital in Stockholm, Sweden.\n\n21 postmenopausal women with primary hyperparathyroidism planned for surgery were included, whereof 15 completed the study protocol. Participants had no disabling comorbidities.\n\nMuscle function tests, muscle biopsies, MRI, and biochemical panels were analyzed before and after parathyroidectomy.\n\nMuscle composition of m. vastus lateralis was tested with MRI and transcriptomic analysis of muscle biopsies. Leg strength was evaluated with timed stands test and peak torque tests. Activity level was estimated from questionnaires.\n\nParathyroidectomy normalized calcium levels (p<0.001) and improved muscle strength (p<0.005). Muscle volume increased (p=0.023) and fat fraction was reduced (p=0.013), without changes in physical activity levels. Transcriptomic analysis identified 981 differentially expressed genes post-surgery, enriched in pathways mirroring exercise-induced adaptations.\n\nThese findings highlight the impact of parathyroidectomy on skeletal muscle function and suggest that muscle assessments should be included in surgical referral criteria to address age-related muscle decline and improve long-term outcomes.", "doi": "10.1210/clinem/dgaf418", "pmid": "40690900", "labels": {"National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Production)": "Service", "NGI Short read": "Service"}, "xrefs": [{"db": "pii", "key": "8210038"}], "notes": [], "created": "2025-11-28T14:57:00.299Z", "modified": "2025-11-28T14:57:00.643Z"}, {"entity": "publication", "iuid": "f59b4fc436324c95a82c883daad1fec8", "links": {"self": {"href": "https://publications.scilifelab.se/publication/f59b4fc436324c95a82c883daad1fec8.json"}, "display": {"href": "https://publications.scilifelab.se/publication/f59b4fc436324c95a82c883daad1fec8"}}, "title": "Proteomic profiles associated with postsurgical progression in non-functioning pituitary adenomas.", "authors": [{"family": "Hall\u00e9n", "given": "Tobias", "initials": "T", "orcid": "0000-0002-3628-7686", "researcher": {"href": "https://publications.scilifelab.se/researcher/3c6c8f5344c943a9ac97cbc7305330d0.json"}}, {"family": "Johannsson", "given": "Gudmundur", "initials": "G", "orcid": "0000-0003-3484-8440", "researcher": {"href": "https://publications.scilifelab.se/researcher/894d22d377534e56a2080c9ee9d511af.json"}}, {"family": "Thorsell", "given": "Annika", "initials": "A"}, {"family": "Olsson", "given": "Daniel S", "initials": "DS", "orcid": "0000-0002-9734-0786", "researcher": {"href": "https://publications.scilifelab.se/researcher/414e7a7567454141be5b9ec473b4fae9.json"}}, {"family": "\u00d6rndal", "given": "Charlotte", "initials": "C"}, {"family": "Engvall", "given": "Angelica", "initials": "A"}, {"family": "Jacobson", "given": "Frida", "initials": "F"}, {"family": "Widgren", "given": "Anna", "initials": "A"}, {"family": "Bergquist", "given": "Jonas", "initials": "J", "orcid": "0000-0002-4597-041X", "researcher": {"href": "https://publications.scilifelab.se/researcher/d745034529f3423abbea230b4e586d20.json"}}, {"family": "Skoglund", "given": "Thomas", "initials": "T", "orcid": "0000-0003-2645-3529", "researcher": {"href": "https://publications.scilifelab.se/researcher/7d18bb0fa7d349798bc3b810a2c5b9d3.json"}}], "type": "journal article", "published": "2023-12-29", "journal": {"title": "J. Clin. Endocrinol. Metab.", "issn": "1945-7197", "issn-l": "0021-972X", "volume": null, "issue": null, "pages": null}, "abstract": "There is a lack of reliable biomarkers capable of predicting postoperative tumor progression of non-functioning pituitary adenomas (NFPAs).\r\n\r\nTo discover proteomic profiles associated with postoperative tumor progression in patients with NFPA.\r\n\r\nCase-controlled exploratory study.\r\n\r\nTertiary university hospital.\r\n\r\nTissue samples were obtained from 46 patients with residual tumor following surgery for NFPA of gonadotroph lineage. Two patient groups were compared: patients requiring reintervention due to residual tumor progression (cases; reintervention group, n=29) and patients with a residual tumor showing no progression for a minimum of 5 years (controls; radiologically stable group, n=17).\r\n\r\nNone.\r\n\r\nDifferentially expressed proteins (DEPs) between patient groups.\r\n\r\nGlobal quantitative proteomic analysis identified 4074 proteins, of which 550 were differentially expressed between the two groups (fold change>80%, false discovery rate-adjusted P\u22640.05). PCA showed good separation between the two groups. Functional enrichment analysis of the DEPs indicated processes involving Translation, ROBO-receptor signaling, Energy metabolism, mRNA metabolism, and RNA splicing. Several upregulated proteins in the reintervention group, including SNRPD1, SRSF10, SWAP-70, and PSMB1, are associated with tumor progression in other cancer types.\r\n\r\nThis is the first exploratory study analyzing proteomic profiles as markers of postoperative tumor progression in NFPA. The findings clearly showed different profiles between tumors with indolent postoperative behavior and those with postoperative tumor progression. Both enriched pathways involving DEPs and specific upregulated proteins have previously been associated with tumor aggressiveness. These results suggest the value of proteomic profiling for predicting tumor progression in patients with NFPA.", "doi": "10.1210/clinem/dgad767", "pmid": "38157275", "labels": {"Glycoproteomics and MS Proteomics": "Collaborative"}, "xrefs": [{"db": "pii", "key": "7503831"}], "notes": [], "created": "2024-01-09T14:47:09.677Z", "modified": "2024-01-16T13:46:27.065Z"}, {"entity": "publication", "iuid": "8735767867ea40119ad8f0fe75671679", "links": {"self": {"href": "https://publications.scilifelab.se/publication/8735767867ea40119ad8f0fe75671679.json"}, "display": {"href": "https://publications.scilifelab.se/publication/8735767867ea40119ad8f0fe75671679"}}, "title": "Serum DHEA and Testosterone Levels Associate Inversely With Coronary Artery Calcification in Elderly Men.", "authors": [{"family": "Ohlsson", "given": "Claes", "initials": "C", "orcid": "0000-0002-9633-2805", "researcher": {"href": "https://publications.scilifelab.se/researcher/995dac358caa4a169fc889b7a3eef44a.json"}}, {"family": "Nethander", "given": "Maria", "initials": "M", "orcid": "0000-0003-3688-906X", "researcher": {"href": "https://publications.scilifelab.se/researcher/53d61951f51c4d40bef24672866382cb.json"}}, {"family": "Norl\u00e9n", "given": "Anna-Karin", "initials": "A"}, {"family": "Poutanen", "given": "Matti", "initials": "M"}, {"family": "Gudmundsson", "given": "Elias Freyr", "initials": "EF"}, {"family": "Aspelund", "given": "Thor", "initials": "T", "orcid": "0000-0002-7998-5433", "researcher": {"href": "https://publications.scilifelab.se/researcher/ceb3e13bc7fa4683b1b11b7d33a01247.json"}}, {"family": "Sigurdsson", "given": "Sigurdur", "initials": "S"}, {"family": "Ryberg", "given": "Henrik", "initials": "H"}, {"family": "Gudnason", "given": "Vilmundur", "initials": "V"}, {"family": "Tivesten", "given": "\u00c5sa", "initials": "\u00c5", "orcid": "0000-0002-8318-0486", "researcher": {"href": "https://publications.scilifelab.se/researcher/55ade4099dfd4859970a6fe21af50870.json"}}], "type": "journal article", "published": "2023-11-17", "journal": {"title": "J. Clin. Endocrinol. Metab.", "issn": "1945-7197", "issn-l": "0021-972X", "volume": "108", "issue": "12", "pages": "3272-3279"}, "abstract": "Epidemiological and preclinical data support cardiovascular, mainly protective, effects of sex steroids in men, but the mechanisms underlying the cardiovascular actions of sex steroids are poorly understood. Vascular calcification parallels the development of atherosclerosis, but is increasingly recognized as a diversified, highly regulated process, which itself may have pathophysiological importance for clinical cardiovascular events.\r\n\r\nTo investigate the association between serum sex steroids and coronary artery calcification (CAC) in elderly men.\r\n\r\nWe used gas chromatography tandem mass spectrometry to analyze a comprehensive sex steroid profile, including levels of dehydroepiandrosterone (DHEA), androstenedione, estrone, testosterone, estradiol, and dihydrotestosterone, in men from the population-based AGES-Reykjavik study (n = 1287, mean 76 years). Further, sex hormone-binding globulin (SHBG) was assayed and bioavailable hormone levels calculated. CAC score was determined by computed tomography. The main outcome measures were cross-sectional associations between dehydroepiandrosterone, androstenedione, estrone, testosterone, dihydrotestosterone, and estradiol and quintiles of CAC.\r\n\r\nSerum levels of DHEA, androstenedione, testosterone, dihydrotestosterone, and bioavailable testosterone showed significant inverse associations with CAC, while estrone, estradiol, bioavailable estradiol, and SHBG did not. DHEA, testosterone, and bioavailable testosterone remained associated with CAC after adjustment for traditional cardiovascular risk factors. In addition, our results support partially independent associations between adrenal-derived DHEA and testes-derived testosterone and CAC.\r\n\r\nSerum levels of DHEA and testosterone are inversely associated with CAC in elderly men, partially independently from each other. These results raise the question whether androgens from both the adrenals and the testes may contribute to male cardiovascular health.", "doi": "10.1210/clinem/dgad351", "pmid": "37391895", "labels": {"Clinical Genomics Gothenburg": "Collaborative", "Clinical Genomics": "Collaborative"}, "xrefs": [{"db": "pmc", "key": "PMC10655543"}, {"db": "pii", "key": "7194268"}], "notes": [], "created": "2023-11-30T22:35:21.935Z", "modified": "2023-11-30T22:37:15.060Z"}, {"entity": "publication", "iuid": "34ad4b4804274e6685480880f7336643", "links": {"self": {"href": "https://publications.scilifelab.se/publication/34ad4b4804274e6685480880f7336643.json"}, "display": {"href": "https://publications.scilifelab.se/publication/34ad4b4804274e6685480880f7336643"}}, "title": "Low Circulating Valine Associate With High Risk of Hip Fractures.", "authors": [{"family": "Grahnemo", "given": "Louise", "initials": "L", "orcid": "0000-0001-5276-6612", "researcher": {"href": "https://publications.scilifelab.se/researcher/bb1ac8fe74954a5db43e8e6538cf8235.json"}}, {"family": "Eriksson", "given": "Anna L", "initials": "AL", "orcid": "0000-0001-5455-2810", "researcher": {"href": "https://publications.scilifelab.se/researcher/538ab065918b4201a2689efc50d2ed2f.json"}}, {"family": "Nethander", "given": "Maria", "initials": "M", "orcid": "0000-0003-3688-906X", "researcher": {"href": "https://publications.scilifelab.se/researcher/53d61951f51c4d40bef24672866382cb.json"}}, {"family": "Johansson", "given": "Robert", "initials": "R"}, {"family": "Lorentzon", "given": "Mattias", "initials": "M", "orcid": "0000-0003-0749-1431", "researcher": {"href": "https://publications.scilifelab.se/researcher/237bc87456e3454082a93f0490c4d4c4.json"}}, {"family": "Mellstr\u00f6m", "given": "Dan", "initials": "D"}, {"family": "Pettersson-Kymmer", "given": "Ulrika", "initials": "U", "orcid": "0000-0002-0557-9803", "researcher": {"href": "https://publications.scilifelab.se/researcher/f3362b7a2ee34c8f9a52261eeb74d636.json"}}, {"family": "Ohlsson", "given": "Claes", "initials": "C", "orcid": "0000-0002-9633-2805", "researcher": {"href": "https://publications.scilifelab.se/researcher/995dac358caa4a169fc889b7a3eef44a.json"}}], "type": "meta-analysis", "published": "2023-10-18", "journal": {"title": "J. Clin. Endocrinol. Metab.", "issn": "1945-7197", "issn-l": "0021-972X", "volume": "108", "issue": "11", "pages": "e1384-e1393"}, "abstract": "Hip fractures constitute a major health concern. An adequate supply of amino acids is crucial to ensure optimal acquisition and remodeling of bone. Circulating amino acid levels have been proposed as markers of bone mineral density, but data on their ability to predict incident fractures are scarce.\r\n\r\nTo investigate the associations between circulating amino acids and incident fractures.\r\n\r\nWe used UK Biobank (n = 111 257; 901 hip fracture cases) as a discovery cohort and the Ume\u00e5 Fracture and Osteoporosis (UFO) hip fracture study (hip fracture cases n = 2225; controls n = 2225) for replication. Associations with bone microstructure parameters were tested in a subsample of Osteoporotic Fractures in Men Sweden (n = 449).\r\n\r\nCirculating valine was robustly associated with hip fractures in the UK Biobank (HR per SD increase 0.79, 95% CI 0.73-0.84), and this finding was replicated in the UFO study (combined meta-analysis including 3126 incident hip fracture cases, odds ratio per SD increase 0.84, 95% CI 0.80-0.88). Detailed bone microstructure analyses showed that high circulating valine was associated with high cortical bone area and trabecular thickness.\r\n\r\nLow circulating valine is a robust predictor of incident hip fractures. We propose that circulating valine may add information for hip fracture prediction. Future studies are warranted to determine whether low valine is causally associated with hip fractures.", "doi": "10.1210/clinem/dgad268", "pmid": "37178220", "labels": {"Clinical Genomics Gothenburg": "Collaborative", "Clinical Genomics": "Collaborative"}, "xrefs": [{"db": "pmc", "key": "PMC10583993"}, {"db": "pii", "key": "7161698"}], "notes": [], "created": "2023-11-30T22:32:36.701Z", "modified": "2023-11-30T22:34:37.285Z"}, {"entity": "publication", "iuid": "5584e86c855f43819255fd1c8610c93a", "links": {"self": {"href": "https://publications.scilifelab.se/publication/5584e86c855f43819255fd1c8610c93a.json"}, "display": {"href": "https://publications.scilifelab.se/publication/5584e86c855f43819255fd1c8610c93a"}}, "title": "Whole-genome Sequencing of Follicular Thyroid Carcinomas Reveal Recurrent Mutations in MicroRNA Processing Subunit DGCR8.", "authors": [{"family": "Paulsson", "given": "Johan O", "initials": "JO", "orcid": "0000-0003-0390-6740", "researcher": {"href": "https://publications.scilifelab.se/researcher/762d22bad5b7462dbba2a87c9b3221a0.json"}}, {"family": "Rafati", "given": "Nima", "initials": "N"}, {"family": "DiLorenzo", "given": "Sebastian", "initials": "S"}, {"family": "Chen", "given": "Yi", "initials": "Y"}, {"family": "Haglund", "given": "Felix", "initials": "F"}, {"family": "Zedenius", "given": "Jan", "initials": "J"}, {"family": "Juhlin", "given": "C Christofer", "initials": "CC", "orcid": "0000-0002-5945-9081", "researcher": {"href": "https://publications.scilifelab.se/researcher/bb660e24421749d4acaaf6e9a90042f8.json"}}], "type": "journal article", "published": "2021-10-21", "journal": {"title": "J. Clin. Endocrinol. Metab.", "issn": "1945-7197", "issn-l": "0021-972X", "volume": "106", "issue": "11", "pages": "3265-3282"}, "abstract": "The genomic and transcriptomic landscape of widely invasive follicular thyroid carcinomas (wiFTCs) and H\u00fcrthle cell carcinoma (HCC) are poorly characterized, and subsets of these tumors lack information on genetic driver events.\n\nThe aim of this study was to bridge this gap.\n\nWe performed whole-genome and RNA sequencing and subsequent bioinformatic analyses of 11 wiFTCs and 2 HCCs with a particularly poor prognosis, and matched normal tissue.\n\nAll wiFTCs exhibited one or several mutations in established thyroid cancer genes, including TERT (n = 4), NRAS (n = 3), HRAS, KRAS, AKT, PTEN, PIK3CA, MUTYH, TSHR, and MEN1 (n = 1 each). MutSig2CV analysis revealed recurrent somatic mutations in FAM72D (n = 3, in 2 wiFTCs and in a single HCC), TP53 (n = 3, in 2 wiFTCs and a single HCC), and EIF1AX (n = 3), with DGCR8 (n = 2) as borderline significant. The DGCR8 mutations were recurrent p.E518K missense alterations, known to cause familial multinodular goiter via disruption of microRNA (miRNA) processing. Expression analyses showed reduced DGCR8 messenger RNA expression in FTCs in general, and the 2 DGCR8 mutants displayed a distinct miRNA profile compared to DGCR8 wild-types. Copy number analyses revealed recurrent gains on chromosomes 4, 6, and 10, and fusion gene analyses revealed 27 high-quality events. Both HCCs displayed hyperploidy, which was fairly unusual in the FTC cohort. Based on the transcriptome data, tumors amassed in 2 principal clusters.\n\nWe describe the genomic and transcriptomic landscape in wiFTCs and HCCs and identify novel recurrent mutations and copy number alterations with possible driver properties and lay the foundation for future studies.", "doi": "10.1210/clinem/dgab471", "pmid": "34171097", "labels": {"Bioinformatics Support, Infrastructure and Training": "Collaborative", "Bioinformatics Support and Infrastructure": "Collaborative", "Bioinformatics Support for Computational Resources": "Service", "Bioinformatics (NBIS)": "Collaborative"}, "xrefs": [{"db": "pii", "key": "6309631"}, {"db": "pmc", "key": "PMC8530729"}], "notes": [], "created": "2021-12-02T14:30:01.594Z", "modified": "2024-01-16T13:48:38.199Z"}, {"entity": "publication", "iuid": "adc9079acc3040a69b2eba909277584d", "links": {"self": {"href": "https://publications.scilifelab.se/publication/adc9079acc3040a69b2eba909277584d.json"}, "display": {"href": "https://publications.scilifelab.se/publication/adc9079acc3040a69b2eba909277584d"}}, "title": "TLR4-Associated IRF-7 and NF\u03baB Signaling Act as a Molecular Link Between Androgen and Metformin Activities and Cytokine Synthesis in the PCOS Endometrium.", "authors": [{"family": "Hu", "given": "Min", "initials": "M"}, {"family": "Zhang", "given": "Yuehui", "initials": "Y"}, {"family": "Li", "given": "Xin", "initials": "X"}, {"family": "Cui", "given": "Peng", "initials": "P"}, {"family": "Sferruzzi-Perri", "given": "Amanda Nancy", "initials": "AN"}, {"family": "Br\u00e4nnstr\u00f6m", "given": "Mats", "initials": "M"}, {"family": "Shao", "given": "Linus R", "initials": "LR"}, {"family": "Billig", "given": "H\u00e5kan", "initials": "H"}], "type": "journal article", "published": "2021-03-25", "journal": {"title": "J. Clin. Endocrinol. Metab.", "issn": "1945-7197", "volume": "106", "issue": "4", "pages": "1022-1040", "issn-l": "0021-972X"}, "abstract": "Low-grade chronic inflammation is commonly seen in polycystic ovary syndrome (PCOS) patients with elevated levels of inflammatory cytokines in the endometrium.\n\nThis work aimed to increase the limited understanding of the mechanisms underlying cytokine synthesis and increased endometrial inflammation in PCOS patients.\n\nEndometrial biopsy samples were collected from non-PCOS (n = 17) and PCOS (n = 22) patients either during the proliferative phase of the menstrual cycle or with hyperplasia. Endometrial explants were prepared from PCOS patients and underwent pharmacological manipulation in vitro. The expression and localization of toll-like receptor 2 (TLR2)/4, key elements of innate immune signal transduction and nuclear factor \u03baB (NF\u03baB) signaling pathways, and multiple cytokines were comprehensively evaluated by Western blotting, immunohistochemistry, and immunofluorescence in endometrial tissues.\n\nWe demonstrated the distribution of protein expression and localization associated with the significantly increased androgen receptor, TLR2, and TLR4-mediated activation of interferon regulatory factor-7 (IRF-7) and NF\u03baB signaling, cytokine production, and endometrial inflammation in PCOS patients compared to non-PCOS patients with and without endometrial hyperplasia. In vitro experiments showed that 5-dihydrotestosterone (DHT) enhanced androgen receptor, TLR4, IRF-7, and p-NF\u03baB p65 protein expression along with increased interferon \u03b1 (IFN\u03b1) and IFN\u0263 abundance. The effects of DHT on IRF-7, p-NF\u03baB p65, and IFN abundance were abolished by flutamide, an antiandrogen. Although 17\u03b2-estradiol (E2) decreased p-IRF-7 expression with little effect on TLR-mediated IRF7 and NF\u03baB signaling or on cytokine protein levels, exposure to metformin alone or in combination with E2 suppressed interleukin-1 receptor-associated kinase 4 (IRAK4), p-IRF-7, IRF-7, I\u03baB kinase \u03b1 (IKK\u03b1), p-NF\u03baB p65, IFN\u0263, and tumor necrosis factor \u03b1 protein expression.\n\nCytokine synthesis and increased endometrial inflammation in PCOS patients are coupled to androgen-induced TLR4/IRF-7/NF\u03baB signaling, which is inhibited by metformin treatment.", "doi": "10.1210/clinem/dgaa951", "pmid": "33382900", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pii", "key": "6056640"}], "notes": [], "created": "2023-02-16T08:16:53.960Z", "modified": "2023-02-16T08:16:53.974Z"}, {"entity": "publication", "iuid": "3553724077584c49885e0ab9f66ec2a2", "links": {"self": {"href": "https://publications.scilifelab.se/publication/3553724077584c49885e0ab9f66ec2a2.json"}, "display": {"href": "https://publications.scilifelab.se/publication/3553724077584c49885e0ab9f66ec2a2"}}, "title": "Glycogenin is Dispensable for Glycogen Synthesis in Human Muscle, and Glycogenin Deficiency Causes Polyglucosan Storage.", "authors": [{"family": "Visuttijai", "given": "Kittichate", "initials": "K", "orcid": "0000-0002-4800-8533", "researcher": {"href": "https://publications.scilifelab.se/researcher/f41f59ad2b0a4e1c95b0cc9cf109f6fa.json"}}, {"family": "Hedberg-Oldfors", "given": "Carola", "initials": "C", "orcid": "0000-0002-7141-4185", "researcher": {"href": "https://publications.scilifelab.se/researcher/dc67028bf0c04f1b9a73bac5e72f9897.json"}}, {"family": "Thomsen", "given": "Christer", "initials": "C"}, {"family": "Glamuzina", "given": "Emma", "initials": "E"}, {"family": "Kornblum", "given": "Cornelia", "initials": "C"}, {"family": "Tasca", "given": "Giorgio", "initials": "G", "orcid": "0000-0003-0849-9144", "researcher": {"href": "https://publications.scilifelab.se/researcher/17e4a6c07f204fb7953350d6b56f3a03.json"}}, {"family": "Hernandez-Lain", "given": "Aurelio", "initials": "A", "orcid": "0000-0002-1933-2238", "researcher": {"href": "https://publications.scilifelab.se/researcher/4b0d26958db04abf8f9240d48a89ec0a.json"}}, {"family": "Sandstedt", "given": "Joakim", "initials": "J", "orcid": "0000-0002-6458-9550", "researcher": {"href": "https://publications.scilifelab.se/researcher/070e186990424c4b83225eb93efc2a66.json"}}, {"family": "Dellgren", "given": "G\u00f6ran", "initials": "G"}, {"family": "Roach", "given": "Peter", "initials": "P"}, {"family": "Oldfors", "given": "Anders", "initials": "A", "orcid": "0000-0003-2523-1414", "researcher": {"href": "https://publications.scilifelab.se/researcher/864bc00c4e234e2aa204e697a9b1d434.json"}}], "type": "journal article", "published": "2020-02-01", "journal": {"title": "J. Clin. Endocrinol. Metab.", "issn": "1945-7197", "volume": "105", "issue": "2", "pages": "557-566", "issn-l": "0021-972X"}, "abstract": "Glycogenin is considered to be an essential primer for glycogen biosynthesis. Nevertheless, patients with glycogenin-1 deficiency due to biallelic GYG1 (NM_004130.3) mutations can store glycogen in muscle. Glycogenin-2 has been suggested as an alternative primer for glycogen synthesis in patients with glycogenin-1 deficiency.\n\nThe objective of this article is to investigate the importance of glycogenin-1 and glycogenin-2 for glycogen synthesis in skeletal and cardiac muscle.\n\nGlycogenin-1 and glycogenin-2 expression was analyzed by Western blot, mass spectrometry, and immunohistochemistry in liver, heart, and skeletal muscle from controls and in skeletal and cardiac muscle from patients with glycogenin-1 deficiency.\n\nGlycogenin-1 and glycogenin-2 both were found to be expressed in the liver, but only glycogenin-1 was identified in heart and skeletal muscle from controls. In patients with truncating GYG1 mutations, neither glycogenin-1 nor glycogenin-2 was expressed in skeletal muscle. However, nonfunctional glycogenin-1 but not glycogenin-2 was identified in cardiac muscle from patients with cardiomyopathy due to GYG1 missense mutations. By immunohistochemistry, the mutated glycogenin-1 colocalized with the storage of glycogen and polyglucosan in cardiomyocytes.\n\nGlycogen can be synthesized in the absence of glycogenin, and glycogenin-1 deficiency is not compensated for by upregulation of functional glycogenin-2. Absence of glycogenin-1 leads to the focal accumulation of glycogen and polyglucosan in skeletal muscle fibers. Expression of mutated glycogenin-1 in the heart is deleterious, and it leads to storage of abnormal glycogen and cardiomyopathy.", "doi": "10.1210/clinem/dgz075", "pmid": "31628455", "labels": {"Glycoproteomics and MS Proteomics": "Service"}, "xrefs": [{"db": "pii", "key": "5599738"}, {"db": "pmc", "key": "PMC7046021"}], "notes": [], "created": "2020-01-30T15:58:42.481Z", "modified": "2024-01-16T13:46:30.988Z"}, {"entity": "publication", "iuid": "74be35950eca40edbc43a331133fbb7d", "links": {"self": {"href": "https://publications.scilifelab.se/publication/74be35950eca40edbc43a331133fbb7d.json"}, "display": {"href": "https://publications.scilifelab.se/publication/74be35950eca40edbc43a331133fbb7d"}}, "title": "Serum Parathyroid Hormone and Risk of Coronary Artery Disease: Exploring Causality Using Mendelian Randomization.", "authors": [{"family": "Melhus", "given": "H\u00e5kan", "initials": "H"}, {"family": "Micha\u00eblsson", "given": "Karl", "initials": "K"}, {"family": "Larsson", "given": "Susanna C", "initials": "SC"}], "type": "journal article", "published": "2019-11-01", "journal": {"volume": "104", "issn": "1945-7197", "issue": "11", "pages": "5595-5600", "title": "J. Clin. Endocrinol. Metab.", "issn-l": "0021-972X"}, "abstract": "Elevated circulating parathyroid hormone concentrations have been associated with increased risk of cardiovascular disease in observational studies, but whether the association is causal is unknown.\n\nWe used the Mendelian randomization design to test whether genetically increased serum parathyroid hormone (S-PTH) concentrations are associated with coronary artery disease (CAD).\n\nFive single-nucleotide polymorphisms robustly associated with S-PTH concentrations were used as instrumental variables to estimate the association of genetically higher S-PTH concentrations with CAD. Summary statistics data for CAD were obtained from a genetic consortium with data from 184,305 individuals (60,801 CAD cases and 123,504 noncases).\n\nOR of CAD per genetically predicted one SD increase of S-PTH concentrations.\n\nGenetically higher S-PTH concentration was not associated with CAD as a whole or myocardial infarction specifically (\u223c70% of total cases). The ORs per genetically predicted one SD increase in S-PTH concentration were 1.01 (95% CI: 0.93 to 1.09; P = 0.88) for CAD and 1.02 (95% CI: 0.94 to 1.10; P = 0.64) for myocardial infarction. The lack of association remained in various sensitivity analyses.\n\nGenetic predisposition to higher S-PTH concentrations does not appear to be an independent risk factor for CAD.", "doi": "10.1210/jc.2019-01063", "pmid": "31310319", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "5532038"}], "notes": [], "created": "2019-10-11T10:29:28.429Z", "modified": "2024-01-16T13:48:43.588Z"}, {"entity": "publication", "iuid": "52812467a6ef42a3a827328042bb65c1", "links": {"self": {"href": "https://publications.scilifelab.se/publication/52812467a6ef42a3a827328042bb65c1.json"}, "display": {"href": "https://publications.scilifelab.se/publication/52812467a6ef42a3a827328042bb65c1"}}, "title": "Transcriptional and Epigenetic Changes Influencing Skeletal Muscle Metabolism in Women With Polycystic Ovary Syndrome.", "authors": [{"family": "Nilsson", "given": "Emma", "initials": "E"}, {"family": "Benrick", "given": "Anna", "initials": "A"}, {"family": "Kokosar", "given": "Milana", "initials": "M"}, {"family": "Krook", "given": "Anna", "initials": "A"}, {"family": "Lindgren", "given": "Eva", "initials": "E"}, {"family": "K\u00e4llman", "given": "Thomas", "initials": "T"}, {"family": "Martis", "given": "Mihaela M", "initials": "MM"}, {"family": "H\u00f8jlund", "given": "Kurt", "initials": "K"}, {"family": "Ling", "given": "Charlotte", "initials": "C"}, {"family": "Stener-Victorin", "given": "Elisabet", "initials": "E"}], "type": "journal article", "published": "2018-12-01", "journal": {"volume": "103", "issn": "1945-7197", "issue": "12", "pages": "4465-4477", "title": "J. Clin. Endocrinol. Metab.", "issn-l": "0021-972X"}, "abstract": "Insulin resistance in skeletal muscle is a major risk factor for the development of type 2 diabetes in women with polycystic ovary syndrome (PCOS). Despite this, the mechanisms underlying insulin resistance in PCOS are largely unknown.\n\nTo investigate the genome-wide DNA methylation and gene expression patterns in skeletal muscle from women with PCOS and controls and relate them to phenotypic variations.\n\nIn a case-control study, skeletal muscle biopsies from women with PCOS (n = 17) and age-, weight-, and body mass index\u2012matched controls (n = 14) were analyzed by array-based DNA methylation and mRNA expression profiling.\n\nEighty-five unique transcripts were differentially expressed in muscle from women with PCOS vs controls, including DYRK1A, SYNPO2, SCP2, and NAMPT. Furthermore, women with PCOS had reduced expression of genes involved in immune system pathways. Two CpG sites showed differential DNA methylation after correction for multiple testing. However, an mRNA expression of \u223c30% of the differentially expressed genes correlated with DNA methylation levels of CpG sites in or near the gene. Functional follow-up studies demonstrated that KLF10 is under transcriptional control of insulin, where insulin promotes glycogen accumulation in myotubes of human muscle cells. Testosterone downregulates the expression levels of COL1A1 and MAP2K6.\n\nPCOS is associated with aberrant skeletal muscle gene expression with dysregulated pathways. Furthermore, we identified specific changes in muscle DNA methylation that may affect gene expression. This study showed that women with PCOS have epigenetic and transcriptional changes in skeletal muscle that, in part, can explain the metabolic abnormalities seen in these women.", "doi": "10.1210/jc.2018-00935", "pmid": "30113663", "labels": {"Bioinformatics Support, Infrastructure and Training": "Collaborative", "Bioinformatics Support and Infrastructure": "Collaborative", "Bioinformatics (NBIS)": "Collaborative"}, "xrefs": [{"db": "pii", "key": "5063490"}], "notes": [], "created": "2019-01-15T08:08:28.581Z", "modified": "2020-01-21T13:53:22.420Z"}, {"entity": "publication", "iuid": "a56ea7ef06e84a569067539347cf845b", "links": {"self": {"href": "https://publications.scilifelab.se/publication/a56ea7ef06e84a569067539347cf845b.json"}, "display": {"href": "https://publications.scilifelab.se/publication/a56ea7ef06e84a569067539347cf845b"}}, "title": "Cytokine Autoantibody Screening in the Swedish Addison Registry Identifies Patients With Undiagnosed APS1", "authors": [{"family": "Eriksson", "given": "Daniel", "initials": "D"}, {"family": "Dalin", "given": "Frida", "initials": "F"}, {"family": "Eriksson", "given": "Gabriel Nordling", "initials": "GN"}, {"family": "Landegren", "given": "Nils", "initials": "N"}, {"family": "Bianchi", "given": "Matteo", "initials": "M"}, {"family": "Hallgren", "given": "\u00c5sa", "initials": "\u00c5"}, {"family": "Dahlqvist", "given": "Per", "initials": "P"}, {"family": "Wahlberg", "given": "Jeanette", "initials": "J"}, {"family": "Ekwall", "given": "Olov", "initials": "O"}, {"family": "Winqvist", "given": "Ola", "initials": "O"}, {"family": "Catrina", "given": "Sergiu Bogdan", "initials": "SB"}, {"family": "R\u00f6nnelid", "given": "Johan", "initials": "J"}, {"family": "Hulting", "given": "Anna Lena", "initials": "AL"}, {"family": "Lindblad-Toh", "given": "Kerstin", "initials": "K", "orcid": "0000-0001-8338-0253", "researcher": {"href": "https://publications.scilifelab.se/researcher/e0063145f7d6476f80ab42f94833f4cf.json"}}, {"family": "Alimohammadi", "given": "Mohammad", "initials": "M"}, {"family": "Husebye", "given": "Eystein S", "initials": "ES"}, {"family": "Knappskog", "given": "Per Morten", "initials": "PM"}, {"family": "Rosengren Pielberg", "given": "Gerli", "initials": "G"}, {"family": "Bensing", "given": "Sophie", "initials": "S"}, {"family": "K\u00e4mpe", "given": "Olle", "initials": "O"}, {"family": "Bensing", "given": "Sophie", "initials": "S"}, {"family": "Hulting", "given": "Anna Lena", "initials": "AL"}, {"family": "Ekwall", "given": "Olov", "initials": "O"}, {"family": "Dahlqvist", "given": "Per", "initials": "P"}, {"family": "Wahlberg", "given": "Jeanette", "initials": "J"}, {"family": "Olsson", "given": "Tommy", "initials": "T"}, {"family": "Kristr\u00f6m", "given": "Berit", "initials": "B"}, {"family": "Laudius", "given": "Maria", "initials": "M"}, {"family": "K\u00e4mpe", "given": "Olle", "initials": "O"}, {"family": "Isaksson", "given": "Magnus", "initials": "M"}, {"family": "Stenlid", "given": "Maria Halldin", "initials": "MH"}, {"family": "Gustafsson", "given": "Jan", "initials": "J"}, {"family": "Gebre-Medhin", "given": "Gennet", "initials": "G"}, {"family": "Bj\u00f6rnsdottir", "given": "Sigridur", "initials": "S"}, {"family": "Eriksson", "given": "Gabriel Nordling", "initials": "GN"}, {"family": "Janson", "given": "Annika", "initials": "A"}, {"family": "\u00c5kerman", "given": "Anna Karin", "initials": "AK"}, {"family": "Bergthorsdottir", "given": "Ragnhildur", "initials": "R"}, {"family": "Johannsson", "given": "Gudmundur", "initials": "G"}, {"family": "Lindskog", "given": "Emma", "initials": "E"}, {"family": "Elfving", "given": "Maria", "initials": "M"}, {"family": "Waldenstr\u00f6m", "given": "Erik", "initials": "E"}, {"family": "Svensson", "given": "Johan", "initials": "J"}, {"family": "Kalcheva", "given": "Zlatka", "initials": "Z"}, {"family": "Eliasson", "given": "Mats", "initials": "M"}, {"family": "Hedman", "given": "Erik", "initials": "E"}, {"family": "Wahlin", "given": "Karin", "initials": "K"}, {"family": "Magnusson", "given": "Anders", "initials": "A"}, {"family": "Ekman", "given": "Bertil", "initials": "B"}, {"family": "Munoz", "given": "Karel Duchen", "initials": "KD"}, {"family": "None", "given": "", "initials": ""}], "type": "journal-article", "published": "2018-01-01", "journal": {"volume": "103", "issn": "0021-972X", "issue": "1", "pages": "179-186", "title": "J. Clin. Endocrinol. Metab.", "issn-l": null}, "abstract": "Autoimmune polyendocrine syndrome type 1 (APS1) is a monogenic disorder that features autoimmune Addison disease as a major component. Although APS1 accounts for only a small fraction of all patients with Addison disease, early identification of these individuals is vital to prevent the potentially lethal complications of APS1.\n\nTo determine whether available serological and genetic markers are valuable screening tools for the identification of APS1 among patients diagnosed with Addison disease.\n\nWe systematically screened 677 patients with Addison disease enrolled in the Swedish Addison Registry for autoantibodies against interleukin-22 and interferon-\u03b14. Autoantibody-positive patients were investigated for clinical manifestations of APS1, additional APS1-specific autoantibodies, and DNA sequence and copy number variations of AIRE.\n\nIn total, 17 patients (2.5%) displayed autoantibodies against interleukin-22 and/or interferon-\u03b14, of which nine were known APS1 cases. Four patients previously undiagnosed with APS1 fulfilled clinical, genetic, and serological criteria. Hence, we identified four patients with undiagnosed APS1 with this screening procedure.\n\nWe propose that patients with Addison disease should be routinely screened for cytokine autoantibodies. Clinical or serological support for APS1 should warrant DNA sequencing and copy number analysis of AIRE to enable early diagnosis and prevention of lethal complications.", "doi": "10.1210/jc.2017-01957", "pmid": "29069385", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [], "notes": [], "created": "2018-04-24T12:29:05.572Z", "modified": "2024-01-16T13:48:47.139Z"}, {"entity": "publication", "iuid": "52c7504764b14dc5a971be1d2f13008d", "links": {"self": {"href": "https://publications.scilifelab.se/publication/52c7504764b14dc5a971be1d2f13008d.json"}, "display": {"href": "https://publications.scilifelab.se/publication/52c7504764b14dc5a971be1d2f13008d"}}, "title": "Acute Sleep Loss Induces Tissue-Specific Epigenetic and Transcriptional Alterations to Circadian Clock Genes in Men.", "authors": [{"family": "Cedernaes", "given": "Jonathan", "initials": "J"}, {"family": "Osler", "given": "Megan E", "initials": "ME"}, {"family": "Voisin", "given": "Sarah", "initials": "S"}, {"family": "Broman", "given": "Jan-Erik", "initials": "JE"}, {"family": "Vogel", "given": "Heike", "initials": "H"}, {"family": "Dickson", "given": "Suzanne L", "initials": "SL"}, {"family": "Zierath", "given": "Juleen R", "initials": "JR"}, {"family": "Schi\u00f6th", "given": "Helgi B", "initials": "HB"}, {"family": "Benedict", "given": "Christian", "initials": "C"}], "type": "journal article", "published": "2015-09-00", "journal": {"volume": "100", "issn": "1945-7197", "issue": "9", "pages": "E1255-E1261", "title": "J. Clin. Endocrinol. Metab.", "issn-l": "0021-972X"}, "abstract": "Shift workers are at increased risk of metabolic morbidities. Clock genes are known to regulate metabolic processes in peripheral tissues, eg, glucose oxidation.\n\nThis study aimed to investigate how clock genes are affected at the epigenetic and transcriptional level in peripheral human tissues following acute total sleep deprivation (TSD), mimicking shift work with extended wakefulness.\n\nIn a randomized, two-period, two-condition, crossover clinical study, 15 healthy men underwent two experimental sessions: x sleep (2230-0700 h) and overnight wakefulness. On the subsequent morning, serum cortisol was measured, followed by skeletal muscle and subcutaneous adipose tissue biopsies for DNA methylation and gene expression analyses of core clock genes (BMAL1, CLOCK, CRY1, PER1). Finally, baseline and 2-h post-oral glucose load plasma glucose concentrations were determined.\n\nIn adipose tissue, acute sleep deprivation vs sleep increased methylation in the promoter of CRY1 (+4%; P = .026) and in two promoter-interacting enhancer regions of PER1 (+15%; P = .036; +9%; P = .026). In skeletal muscle, TSD vs sleep decreased gene expression of BMAL1 (-18%; P = .033) and CRY1 (-22%; P = .047). Concentrations of serum cortisol, which can reset peripheral tissue clocks, were decreased (2449 \u00b1 932 vs 3178 \u00b1 723 nmol/L; P = .039), whereas postprandial plasma glucose concentrations were elevated after TSD (7.77 \u00b1 1.63 vs 6.59 \u00b1 1.32 mmol/L; P = .011).\n\nOur findings demonstrate that a single night of wakefulness can alter the epigenetic and transcriptional profile of core circadian clock genes in key metabolic tissues. Tissue-specific clock alterations could explain why shift work may disrupt metabolic integrity as observed herein.", "doi": "10.1210/JC.2015-2284", "pmid": "26168277", "labels": {"National Genomics Infrastructure": null, "NGI Uppsala (SNP&SEQ Technology Platform)": null}, "xrefs": [{"db": "ClinicalTrials.gov", "key": "NCT01800253"}], "notes": [], "created": "2017-05-02T12:56:43.222Z", "modified": "2020-01-21T13:56:02.314Z"}, {"entity": "publication", "iuid": "8a7b8e5545af42fe83c2bdc222607eca", "links": {"self": {"href": "https://publications.scilifelab.se/publication/8a7b8e5545af42fe83c2bdc222607eca.json"}, "display": {"href": "https://publications.scilifelab.se/publication/8a7b8e5545af42fe83c2bdc222607eca"}}, "title": "Somatic mutations in H-RAS in sporadic pheochromocytoma and paraganglioma identified by exome sequencing.", "authors": [{"family": "Crona", "given": "Joakim", "initials": "J"}, {"family": "Delgado Verdugo", "given": "Alberto", "initials": "A"}, {"family": "Maharjan", "given": "Rajani", "initials": "R"}, {"family": "St\u00e5lberg", "given": "Peter", "initials": "P"}, {"family": "Granberg", "given": "Dan", "initials": "D"}, {"family": "Hellman", "given": "Per", "initials": "P"}, {"family": "Bj\u00f6rklund", "given": "Peyman", "initials": "P"}], "type": "journal article", "published": "2013-07-00", "journal": {"volume": "98", "issn": "1945-7197", "issue": "7", "pages": "E1266-E1271", "title": "J. Clin. Endocrinol. Metab.", "issn-l": "0021-972X"}, "abstract": "Up to 60% of pheochromocytoma (PCC) and paraganglioma (PGL) are associated with either somatic or germline mutations in established PCC and PGL susceptibility loci. Most unexplained cases are characterized by an increased activity of the RAS/RAF/ERK signaling pathway. Mutations in RAS subtypes H, K, and N are common in human cancers; however, previous studies have been inconsistent regarding the mutational status of RAS in PCC and PGL.\n\nThe aim of this study was to identify novel disease causing genes in PCC and PGL tumors.\n\nFour benign and sporadic PCC and PGL tumors were subjected to whole exome sequencing using the Illumina HiSeq Platform. Sequences were processed by CLC genomics 4.9 bioinformatics software and the acquired list of genetic variants was filtered against the Catalogue of Somatic Mutations in Cancer database. Findings were validated in an additional 78 PCC and PGL tumor lesions.\n\nExome sequencing identified 2 cases with somatic mutations in the H-RAS. In total, 6.9% (n = 4/58) of tumors negative for mutations in major PCC and PGL loci had mutations in H-RAS: G13R, Q61K, and Q61R. There were 3 PCC and 1 PGL; all had sporadic presentation with benign tumor characteristics and substantial increases in norepinephrine and/or epinephrine. H-RAS tumors were exclusively found in male patients (P = .007).\n\nWe identified recurrent somatic H-RAS mutations in pheochromocytoma and paraganglioma. Tumors with H-RAS mutations had activation of the RAS/RAF/ERK signaling pathway and were associated with male PCC patients having benign and sporadic disease characteristics. H-RAS could serve as a prognostic and predictive marker as well as a novel therapeutic target.", "doi": "10.1210/jc.2012-4257", "pmid": "23640968", "labels": {"National Genomics Infrastructure": null, "NGI Uppsala (SNP&SEQ Technology Platform)": null}, "xrefs": [{"db": "pii", "key": "jc.2012-4257"}], "notes": [], "created": "2017-05-04T15:01:20.041Z", "modified": "2020-01-21T13:56:03.543Z"}, {"entity": "publication", "iuid": "752ae511ee974720af3eb8a3ba277f87", "links": {"self": {"href": "https://publications.scilifelab.se/publication/752ae511ee974720af3eb8a3ba277f87.json"}, "display": {"href": "https://publications.scilifelab.se/publication/752ae511ee974720af3eb8a3ba277f87"}}, "title": "Adipose tissue resting energy expenditure and expression of genes involved in mitochondrial function are higher in women than in men.", "authors": [{"family": "Nookaew", "given": "Intawat", "initials": "I"}, {"family": "Svensson", "given": "Per-Arne", "initials": "PA"}, {"family": "Jacobson", "given": "Peter", "initials": "P"}, {"family": "Jern\u00e5s", "given": "Margareta", "initials": "M"}, {"family": "Taube", "given": "Magdalena", "initials": "M"}, {"family": "Larsson", "given": "Ingrid", "initials": "I"}, {"family": "Andersson-Assarsson", "given": "Johanna C", "initials": "JC"}, {"family": "Sj\u00f6str\u00f6m", "given": "Lars", "initials": "L"}, {"family": "Froguel", "given": "Philippe", "initials": "P"}, {"family": "Walley", "given": "Andrew", "initials": "A"}, {"family": "Nielsen", "given": "Jens", "initials": "J", "orcid": "0000-0002-9955-6003", "researcher": {"href": "https://publications.scilifelab.se/researcher/7a596e289be4438a8a2653b1f25fea8b.json"}}, {"family": "Carlsson", "given": "Lena M S", "initials": "LM"}], "type": "journal article", "published": "2013-02-00", "journal": {"volume": "98", "issn": "1945-7197", "issue": "2", "pages": "E370-E378", "title": "J. Clin. Endocrinol. Metab.", "issn-l": "0021-972X"}, "abstract": "Men and women differ in body fat distribution and adipose tissue metabolism as well as in obesity comorbidities and their response to obesity treatment.\n\nThe objective of the study was a search for sex differences in adipose tissue function.\n\nThis was an exploratory study performed at a university hospital.\n\nResting metabolic rate (RMR), body composition, and sc adipose tissue genome-wide expression were measured in the SOS Sib Pair study (n = 732).\n\nThe relative contribution of fat mass to RMR and the metabolic rate per kilogram adipose tissue was higher in women than in men (P value for sex by fat mass interaction = .0019). Women had increased expression of genes involved in mitochondrial function, here referred to as a mitochondrial gene signature. Analysis of liver, muscle, and blood showed that the pronounced mitochondrial gene signature in women was specific for adipose tissue. Brown adipocytes are dense in mitochondria, and the expression of the brown adipocyte marker uncoupling protein 1 was 5-fold higher in women compared with men in the SOS Sib Pair Study (P = 7.43 \u00d7 10(-7)), and this was confirmed in a cross-sectional, population-based study (n = 83, 6-fold higher in women, P = .00256).\n\nThe increased expression of the brown adipocyte marker uncoupling protein 1 in women indicates that the higher relative contribution of the fat mass to RMR in women is in part explained by an increased number of brown adipocytes.", "doi": "10.1210/jc.2012-2764", "pmid": "23264395", "labels": {"Bioinformatics Support, Infrastructure and Training": null, "Bioinformatics Support and Infrastructure": null, "Bioinformatics (NBIS)": ""}, "xrefs": [{"db": "pii", "key": "jc.2012-2764"}, {"db": "pmc", "key": "PMC3633773"}], "notes": [], "created": "2017-05-04T14:56:24.579Z", "modified": "2021-07-05T13:05:37.674Z"}, {"entity": "publication", "iuid": "aefd890bfba14f1c884cfa73bfe11a17", "links": {"self": {"href": "https://publications.scilifelab.se/publication/aefd890bfba14f1c884cfa73bfe11a17.json"}, "display": {"href": "https://publications.scilifelab.se/publication/aefd890bfba14f1c884cfa73bfe11a17"}}, "title": "Variants in STAT5B associate with serum TC and LDL-C levels.", "authors": [{"family": "Kornfeld", "given": "Jan-Wilhelm", "initials": "JW"}, {"family": "Isaacs", "given": "Aaron", "initials": "A"}, {"family": "Vitart", "given": "Veronique", "initials": "V"}, {"family": "Pospisilik", "given": "J Andrew", "initials": "JA"}, {"family": "Meitinger", "given": "Thomas", "initials": "T"}, {"family": "Gyllensten", "given": "Ulf", "initials": "U"}, {"family": "Wilson", "given": "James F", "initials": "JF"}, {"family": "Rudan", "given": "Igor", "initials": "I"}, {"family": "Campbell", "given": "Harry", "initials": "H"}, {"family": "Penninger", "given": "Josef M", "initials": "JM"}, {"family": "Sexl", "given": "Veronika", "initials": "V"}, {"family": "Moriggl", "given": "Richard", "initials": "R"}, {"family": "van Duijn", "given": "Cornelia", "initials": "C"}, {"family": "Pramstaller", "given": "Peter P", "initials": "PP"}, {"family": "Hicks", "given": "Andrew A", "initials": "AA"}], "type": "journal article", "published": "2011-09-00", "journal": {"volume": "96", "issn": "1945-7197", "issue": "9", "pages": "E1496-E1501", "title": "J. Clin. Endocrinol. Metab.", "issn-l": "0021-972X"}, "abstract": "Known genetic variants influencing serum lipid levels do not adequately account for the observed population variability of these phenotypes. The GH/signal transducers and activators of transcription (STAT) signaling pathway is an evolutionary conserved system that exerts strong effects on metabolism, including that of lipids.\n\nWe analyzed the association of 11 single-nucleotide polymorphisms (SNP) spanning the STAT5B/STAT5A/STAT3 locus with serum lipid levels in six European populations (n = 5162 nondiabetic individuals).\n\nAfter adjustment for age, sex, alcohol use, smoking, and body mass index, we identified STAT5B variants (rs8082391 and rs8064638) in novel association with total cholesterol (TC; P = 0.001 and P = 0.002) and low-density lipoprotein cholesterol (P = 0.002 and P = 0.004) levels. The minor alleles of these single-nucleotide polymorphisms were significantly enriched in hyperlipidemic individuals across the six discovery populations (P = 0.004 and P = 0.006). In transgenic mice deficient for hepatic STAT5A and STAT5B, reduced serum TC levels coincided with reduced hepatic cholesterol biosynthesis as demonstrated using gene expression profiling and pathway enrichment analysis.\n\nGenetic variants in STAT5B are associated with TC and low-density lipoprotein cholesterol levels among six populations. Mechanistically, STAT5B transcriptionally regulates hepatic cholesterol homeostasis.", "doi": "10.1210/jc.2011-0322", "pmid": "21752895", "labels": {"National Genomics Infrastructure": null, "NGI Uppsala (Uppsala Genome Center)": null}, "xrefs": [{"db": "pii", "key": "jc.2011-0322"}], "notes": [], "created": "2017-05-04T15:01:59.199Z", "modified": "2020-01-21T13:56:04.609Z"}, {"entity": "publication", "iuid": "6dae4cf24e97417fb0750005bffeca6c", "links": {"self": {"href": "https://publications.scilifelab.se/publication/6dae4cf24e97417fb0750005bffeca6c.json"}, "display": {"href": "https://publications.scilifelab.se/publication/6dae4cf24e97417fb0750005bffeca6c"}}, "title": "Genetic association and gene expression analysis identify FGFR1 as a new susceptibility gene for human obesity.", "authors": [{"family": "Jiao", "given": "Hong", "initials": "H"}, {"family": "Arner", "given": "Peter", "initials": "P"}, {"family": "Dickson", "given": "Suzanne L", "initials": "SL"}, {"family": "Vidal", "given": "Hubert", "initials": "H"}, {"family": "Mejhert", "given": "Niklas", "initials": "N"}, {"family": "Henegar", "given": "Corneliu", "initials": "C"}, {"family": "Taube", "given": "Magdalena", "initials": "M"}, {"family": "Hansson", "given": "Caroline", "initials": "C"}, {"family": "Hinney", "given": "Anke", "initials": "A"}, {"family": "Galan", "given": "Pilar", "initials": "P"}, {"family": "Simon", "given": "Chantal", "initials": "C"}, {"family": "Silveira", "given": "Angela", "initials": "A"}, {"family": "Benrick", "given": "Anna", "initials": "A"}, {"family": "Jansson", "given": "John-Olov", "initials": "JO"}, {"family": "Bouloumi\u00e9", "given": "Anne", "initials": "A"}, {"family": "Langin", "given": "Dominique", "initials": "D"}, {"family": "Laville", "given": "Martine", "initials": "M"}, {"family": "Debard", "given": "Cyrille", "initials": "C"}, {"family": "Axelsson", "given": "Tomas", "initials": "T"}, {"family": "Ryd\u00e9n", "given": "Mikael", "initials": "M"}, {"family": "Kere", "given": "Juha", "initials": "J"}, {"family": "Dahlman-Wright", "given": "Karin", "initials": "K"}, {"family": "Hamsten", "given": "Anders", "initials": "A"}, {"family": "Clement", "given": "Karine", "initials": "K"}, {"family": "Dahlman", "given": "Ingrid", "initials": "I"}], "type": "journal article", "published": "2011-06-00", "journal": {"volume": "96", "issn": "1945-7197", "issue": "6", "pages": "E962-E966", "title": "J. Clin. Endocrinol. Metab.", "issn-l": "0021-972X"}, "abstract": "Previous studies suggest a role for fibroblast growth factor receptor 1 (FGFR1) in the regulation of energy balance.\n\nOur objective was to investigate whether FGFR1 is an obesity gene by genetic association and functional studies.\n\nThe study was designed to genotype common FGFR1 single-nucleotide polymorphisms (SNP) in large cohorts, confirm significant results in additional cohorts, and measure FGFR1 expression in human adipose tissue and in rodent hypothalamus.\n\nGeneral community and referral centers for specialized care was the setting for the study.\n\nWe genotyped FGFR1 SNP in 2438 obese and 2115 lean adults and 985 obese and 532 population-based children. Results were confirmed in 928 obese and 2738 population-based adults and 487 obese and 441 lean children. Abdominal sc adipose tissue was investigated in 202 subjects. We also investigated diet-induced, obese fasting, and fed rats.\n\nWe analyzed the association between FGFR1 SNP and obesity. In secondary analyses, we related adipose FGFR1 expression to genotype, obesity, and degree of fat cell differentiation and related hypothalamic FGFR1 to energy balance.\n\nFGFR1 rs7012413*T was nominally associated with obesity in all four cohorts; metaanalysis odds ratio = 1.17 (95% confidence interval = 1.10-1.25), and P = 1.8 \u00d7 10(-6), which was P = 7.0 \u00d7 10(-8) in the recessive model. rs7012413*T was associated with FGFR1 expression in adipose tissue (P < 0.0001). In this organ, but not in skeletal muscle, FGFR1 mRNA (P < 0.0001) and protein (P < 0.05) were increased in obesity. In rats, hypothalamic expression of FGFR1 declined after fasting (P < ]0.001) and increased after diet-induced obesity (P < 0.05).\n\nFGFR1 is a novel obesity gene that may promote obesity by influencing adipose tissue and the hypothalamic control of appetite.", "doi": "10.1210/jc.2010-2639", "pmid": "21430024", "labels": {"National Genomics Infrastructure": null, "Mutation Analysis Facility (MAF)": null, "Bioinformatics and Expression Analysis (BEA)": null, "NGI Uppsala (SNP&SEQ Technology Platform)": null}, "xrefs": [{"db": "pii", "key": "jc.2010-2639"}], "notes": [], "created": "2017-05-04T15:00:47.347Z", "modified": "2020-01-21T13:56:02.867Z"}, {"entity": "publication", "iuid": "502a7a8e7d64496aa6c1aac673caa148", "links": {"self": {"href": "https://publications.scilifelab.se/publication/502a7a8e7d64496aa6c1aac673caa148.json"}, "display": {"href": "https://publications.scilifelab.se/publication/502a7a8e7d64496aa6c1aac673caa148"}}, "title": "Mapping of the fibroblast growth factors in human white adipose tissue.", "authors": [{"family": "Mejhert", "given": "Niklas", "initials": "N"}, {"family": "Galitzky", "given": "Jean", "initials": "J"}, {"family": "Pettersson", "given": "Amanda T", "initials": "AT"}, {"family": "Bambace", "given": "Clara", "initials": "C"}, {"family": "Blomqvist", "given": "Lennart", "initials": "L"}, {"family": "Bouloumi\u00e9", "given": "Anne", "initials": "A"}, {"family": "Frayn", "given": "Keith N", "initials": "KN"}, {"family": "Dahlman", "given": "Ingrid", "initials": "I"}, {"family": "Arner", "given": "Peter", "initials": "P"}, {"family": "Ryd\u00e9n", "given": "Mikael", "initials": "M"}], "type": "journal article", "published": "2010-05-00", "journal": {"volume": "95", "issn": "1945-7197", "issue": "5", "pages": "2451-2457", "title": "J. Clin. Endocrinol. Metab.", "issn-l": "0021-972X"}, "abstract": "Fibroblast growth factors (FGFs) regulate the development of white adipose tissue (WAT). However, the secretion and cellular origin of individual FGFs in WAT as well as the influence of obesity are unknown.\n\nOur objective was to map FGFs in human sc WAT, the cellular source, and association with obesity.\n\nSecretion, mRNA, and circulatory levels of FGFs in human abdominal sc WAT from nonobese and obese donors were examined by microarray, real-time quantitative PCR, and ELISA. The activity of FGFs in cultured human adipocytes was determined by phosphorylation assays.\n\nExpression of five FGFs (FGF1, FGF2, FGF7, FGF9, and FGF18) and FGF homologous factor (FHF2) was identified in WAT. Only FGF1 was released in a time-dependent manner from sc WAT, and fat cells were the major source of FGF1 secretion. FGF1 expression increased and FGF2 decreased during adipocyte differentiation. Furthermore, FGF1 was not secreted into the circulation. Although FGF1 levels were 2-fold increased in obesity, they were unaltered by weight reduction. Only FGF1 and FGF2 induced a marked concentration-dependent phosphorylation of p44/42 in cultured human adipocytes.\n\nOf the investigated FGFs, only FGF1 is secreted from sc WAT and predominantly so from the adipocyte fraction. The activity in adipocyte cultures and lack of secretion into the circulation suggest that FGF1 acts as an auto- or paracrine factor. FGF1 levels are increased in obesity but unaffected by weight reduction, suggesting a primary defect in obese individuals. In conclusion, FGF1 may play a superior role among the FGFs in sc WAT and obesity development.", "doi": "10.1210/jc.2009-2049", "pmid": "20228166", "labels": {"Bioinformatics and Expression Analysis (BEA)": null}, "xrefs": [{"db": "pii", "key": "jc.2009-2049"}], "notes": [], "created": "2017-05-04T15:03:06.325Z", "modified": "2017-05-30T12:39:14.624Z"}], "created": "2017-05-09T09:12:15.545Z", "modified": "2020-11-27T13:14:08.426Z"}