{"entity": "researcher", "timestamp": "2026-08-09T07:58:06.841Z", "family": "Pilon", "given": "Marc", "initials": "M", "orcid": "0000-0003-3919-2882", "affiliations": [], "links": {"self": {"href": "https://publications.scilifelab.se/researcher/d45c4ecf9afe463c971af2de53a770a8.json"}, "display": {"href": "https://publications.scilifelab.se/researcher/d45c4ecf9afe463c971af2de53a770a8"}}, "publications": [{"entity": "publication", "iuid": "a28a213490064713ad542662610169a6", "links": {"self": {"href": "https://publications.scilifelab.se/publication/a28a213490064713ad542662610169a6.json"}, "display": {"href": "https://publications.scilifelab.se/publication/a28a213490064713ad542662610169a6"}}, "title": "Aging AdipoR2-deficient mice are hyperactive with enlarged brains excessively rich in saturated fatty acids.", "authors": [{"family": "Ruiz", "given": "Mario", "initials": "M", "orcid": "0000-0002-7149-6600", "researcher": {"href": "https://publications.scilifelab.se/researcher/35ea5372ccf64bad864d90e4b3698a24.json"}}, {"family": "Devkota", "given": "Ranjan", "initials": "R", "orcid": "0009-0001-6289-7891", "researcher": {"href": "https://publications.scilifelab.se/researcher/28f5086847c74fafbecac69a028f14a4.json"}}, {"family": "Bergh", "given": "Per-Olof", "initials": "PO", "orcid": "0000-0001-9993-6965", "researcher": {"href": "https://publications.scilifelab.se/researcher/28c1f37dc6cc4ed98c8e8eb1a621fa2c.json"}}, {"family": "Nik", "given": "Ali Moussavi", "initials": "AM"}, {"family": "Blid Sk\u00f6ldheden", "given": "Sebastian", "initials": "S"}, {"family": "Mondejar-Duran", "given": "Jorge", "initials": "J"}, {"family": "Tufvesson-Alm", "given": "Maximilian", "initials": "M"}, {"family": "Bohlooly-Y", "given": "Mohammad", "initials": "M"}, {"family": "Sanchez", "given": "Diego", "initials": "D"}, {"family": "Carlsson", "given": "Peter", "initials": "P"}, {"family": "Henricsson", "given": "Marcus", "initials": "M", "orcid": "0000-0002-4202-0339", "researcher": {"href": "https://publications.scilifelab.se/researcher/01a323cbf0a24269bd32bfc34539e021.json"}}, {"family": "Jerlhag", "given": "Elisabet", "initials": "E", "orcid": "0000-0003-2408-3165", "researcher": {"href": "https://publications.scilifelab.se/researcher/072e685dbffe46a4aa857740467e867a.json"}}, {"family": "Bor\u00e9n", "given": "Jan", "initials": "J", "orcid": "0000-0003-0786-8091", "researcher": {"href": "https://publications.scilifelab.se/researcher/1e85f6d287ce4c60a7b35b287efb4f79.json"}}, {"family": "Pilon", "given": "Marc", "initials": "M", "orcid": "0000-0003-3919-2882", "researcher": {"href": "https://publications.scilifelab.se/researcher/d45c4ecf9afe463c971af2de53a770a8.json"}}], "type": "journal article", "published": "2024-07-31", "journal": {"title": "FASEB J.", "issn": "1530-6860", "volume": "38", "issue": "14", "pages": "e23815", "issn-l": "0892-6638"}, "abstract": "To investigate how the fatty acid composition of brain phospholipids influences brain-specific processes, we leveraged the AdipoR2 (adiponectin receptor 2) knockout mouse model in which the brain is enlarged, and cellular membranes are excessively rich in saturated fatty acids. Lipidomics analysis of brains at 2, 7, and 18 months of age showed that phosphatidylcholines, which make up about two-thirds of all cerebrum membrane lipids, contain a gross excess of saturated fatty acids in AdipoR2 knockout mice, and that this is mostly attributed to an excess palmitic acid (C16:0) at the expense of oleic acid (C18:1), consistent with a defect in fatty acid desaturation and elongation in the mutant. Specifically, there was a ~12% increase in the overall saturated fatty acid content within phosphatidylcholines and a ~30% increase in phosphatidylcholines containing two palmitic acids. Phosphatidylethanolamines, sphingomyelins, ceramides, lactosylceramides, and dihydroceramides also showed an excess of saturated fatty acids in the AdipoR2 knockout mice while nervonic acid (C24:1) was enriched at the expense of shorter saturated fatty acids in glyceroceramides. Similar defects were found in the cerebellum and myelin sheaths. Histology showed that cell density is lower in the cerebrum of AdipoR2 knockout mice, but electron microscopy did not detect reproducible defects in the ultrastructure of cerebrum neurons, though proteomics analysis showed an enrichment of electron transport chain proteins in the cerebellum. Behavioral tests showed that older (33 weeks old) AdipoR2 knockout mice are hyperactive and anxious compared to control mice of a similar age. Also, in contrast to control mice, the AdipoR2 knockout mice do not gain weight in old age but do have normal lifespans. We conclude that an excess fatty acid saturation in brain phospholipids is accompanied by hyperactivity but seems otherwise well tolerated.", "doi": "10.1096/fj.202400293RR", "pmid": "38989587", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [], "notes": [], "created": "2024-11-15T12:10:51.341Z", "modified": "2024-11-15T12:10:51.835Z"}, {"entity": "publication", "iuid": "e02d48d0f6b647e8baf207b0270fd127", "links": {"self": {"href": "https://publications.scilifelab.se/publication/e02d48d0f6b647e8baf207b0270fd127.json"}, "display": {"href": "https://publications.scilifelab.se/publication/e02d48d0f6b647e8baf207b0270fd127"}}, "title": "Elevated Adipocyte Membrane Phospholipid Saturation Does Not Compromise Insulin Signaling.", "authors": [{"family": "Palmgren", "given": "Henrik", "initials": "H"}, {"family": "Petkevicius", "given": "Kasparas", "initials": "K"}, {"family": "Bartesaghi", "given": "Stefano", "initials": "S"}, {"family": "Ahnmark", "given": "Andrea", "initials": "A"}, {"family": "Ruiz", "given": "Mario", "initials": "M"}, {"family": "Nilsson", "given": "Ralf", "initials": "R"}, {"family": "L\u00f6fgren", "given": "Lars", "initials": "L"}, {"family": "Glover", "given": "Matthew S", "initials": "MS"}, {"family": "Andr\u00e9asson", "given": "Anne-Christine", "initials": "AC"}, {"family": "Andersson", "given": "Liselotte", "initials": "L"}, {"family": "Becquart", "given": "C\u00e9cile", "initials": "C"}, {"family": "Kurczy", "given": "Michael", "initials": "M"}, {"family": "Kull", "given": "Bengt", "initials": "B"}, {"family": "Wallin", "given": "Simonetta", "initials": "S"}, {"family": "Karlsson", "given": "Daniel", "initials": "D"}, {"family": "Hess", "given": "Sonja", "initials": "S"}, {"family": "Maresca", "given": "Marcello", "initials": "M"}, {"family": "Bohlooly-Y", "given": "Mohammad", "initials": "M"}, {"family": "Peng", "given": "Xiao-Rong", "initials": "XR"}, {"family": "Pilon", "given": "Marc", "initials": "M", "orcid": "0000-0003-3919-2882", "researcher": {"href": "https://publications.scilifelab.se/researcher/d45c4ecf9afe463c971af2de53a770a8.json"}}], "type": "journal article", "published": "2023-10-01", "journal": {"title": "Diabetes", "issn": "1939-327X", "volume": "72", "issue": "10", "pages": "1350-1363", "issn-l": "0012-1797"}, "abstract": "Increased saturated fatty acid (SFA) levels in membrane phospholipids have been implicated in the development of metabolic disease. Here, we tested the hypothesis that increased SFA content in cell membranes negatively impacts adipocyte insulin signaling. Preadipocyte cell models with elevated SFA levels in phospholipids were generated by disrupting the ADIPOR2 locus, which resulted in a striking twofold increase in SFA-containing phosphatidylcholines and phosphatidylethanolamines, which persisted in differentiated adipocytes. Similar changes in phospholipid composition were observed in white adipose tissues isolated from the ADIPOR2-knockout mice. The SFA levels in phospholipids could be further increased by treating ADIPOR2-deficient cells with palmitic acid and resulted in reduced membrane fluidity and endoplasmic reticulum stress in mouse and human preadipocytes. Strikingly, increased SFA levels in differentiated adipocyte phospholipids had no effect on adipocyte gene expression or insulin signaling in vitro. Similarly, increased adipocyte phospholipid saturation did not impair white adipose tissue function in vivo, even in mice fed a high-saturated fat diet at thermoneutrality. We conclude that increasing SFA levels in adipocyte phospholipids is well tolerated and does not affect adipocyte insulin signaling in vitro and in vivo.", "doi": "10.2337/db22-0293", "pmid": "36580483", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC10545576"}, {"db": "pii", "key": "148231"}], "notes": [], "created": "2023-12-01T10:49:13.271Z", "modified": "2023-12-01T10:49:46.691Z"}, {"entity": "publication", "iuid": "452f9e423170414ea771ee32215c63e1", "links": {"self": {"href": "https://publications.scilifelab.se/publication/452f9e423170414ea771ee32215c63e1.json"}, "display": {"href": "https://publications.scilifelab.se/publication/452f9e423170414ea771ee32215c63e1"}}, "title": "Sphingosine 1-phosphate mediates adiponectin receptor signaling essential for lipid homeostasis and embryogenesis.", "authors": [{"family": "Ruiz", "given": "Mario", "initials": "M", "orcid": "0000-0002-7149-6600", "researcher": {"href": "https://publications.scilifelab.se/researcher/35ea5372ccf64bad864d90e4b3698a24.json"}}, {"family": "Devkota", "given": "Ranjan", "initials": "R"}, {"family": "Panagaki", "given": "Dimitra", "initials": "D"}, {"family": "Bergh", "given": "Per-Olof", "initials": "PO", "orcid": "0000-0001-9993-6965", "researcher": {"href": "https://publications.scilifelab.se/researcher/28c1f37dc6cc4ed98c8e8eb1a621fa2c.json"}}, {"family": "Kaper", "given": "Delaney", "initials": "D", "orcid": "0000-0002-9929-8104", "researcher": {"href": "https://publications.scilifelab.se/researcher/e96d29226c884ec496240844de56499a.json"}}, {"family": "Henricsson", "given": "Marcus", "initials": "M", "orcid": "0000-0002-4202-0339", "researcher": {"href": "https://publications.scilifelab.se/researcher/01a323cbf0a24269bd32bfc34539e021.json"}}, {"family": "Nik", "given": "Ali", "initials": "A"}, {"family": "Petkevicius", "given": "Kasparas", "initials": "K", "orcid": "0000-0003-2295-6065", "researcher": {"href": "https://publications.scilifelab.se/researcher/d807cea22e324d8297776e90d31ed636.json"}}, {"family": "H\u00f6\u00f6g", "given": "Johanna L", "initials": "JL", "orcid": "0000-0003-2162-3816", "researcher": {"href": "https://publications.scilifelab.se/researcher/f1eaedff964f4060ae6e69f59cad4521.json"}}, {"family": "Bohlooly-Y", "given": "Mohammad", "initials": "M"}, {"family": "Carlsson", "given": "Peter", "initials": "P"}, {"family": "Bor\u00e9n", "given": "Jan", "initials": "J", "orcid": "0000-0003-0786-8091", "researcher": {"href": "https://publications.scilifelab.se/researcher/1e85f6d287ce4c60a7b35b287efb4f79.json"}}, {"family": "Pilon", "given": "Marc", "initials": "M", "orcid": "0000-0003-3919-2882", "researcher": {"href": "https://publications.scilifelab.se/researcher/d45c4ecf9afe463c971af2de53a770a8.json"}}], "type": "journal article", "published": "2022-11-22", "journal": {"title": "Nat Commun", "issn": "2041-1723", "volume": "13", "issue": "1", "pages": "7162", "issn-l": "2041-1723"}, "abstract": "Cells and organisms require proper membrane composition to function and develop. Phospholipids are the major component of membranes and are primarily acquired through the diet. Given great variability in diet composition, cells must be able to deploy mechanisms that correct deviations from optimal membrane composition and properties. Here, using lipidomics and unbiased proteomics, we found that the embryonic lethality in mice lacking the fluidity regulators Adiponectin Receptors 1 and 2 (AdipoR1/2) is associated with aberrant high saturation of the membrane phospholipids. Using mouse embryonic fibroblasts (MEFs) derived from AdipoR1/2-KO embryos, human cell lines and the model organism C. elegans we found that, mechanistically, AdipoR1/2-derived sphingosine 1-phosphate (S1P) signals in parallel through S1PR3-SREBP1 and PPAR\u03b3 to sustain the expression of the fatty acid desaturase SCD and maintain membrane properties. Thus, our work identifies an evolutionary conserved pathway by which cells and organisms achieve membrane homeostasis and adapt to a variable environment.", "doi": "10.1038/s41467-022-34931-0", "pmid": "36418331", "labels": {"Glycoproteomics and MS Proteomics": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC9684441"}, {"db": "pii", "key": "10.1038/s41467-022-34931-0"}], "notes": [], "created": "2023-03-07T14:34:55.175Z", "modified": "2024-01-16T13:46:28.029Z"}, {"entity": "publication", "iuid": "8b71ca4979984436acd61a92e09fef83", "links": {"self": {"href": "https://publications.scilifelab.se/publication/8b71ca4979984436acd61a92e09fef83.json"}, "display": {"href": "https://publications.scilifelab.se/publication/8b71ca4979984436acd61a92e09fef83"}}, "title": "TLCD1 and TLCD2 regulate cellular phosphatidylethanolamine composition and promote the progression of non-alcoholic steatohepatitis", "authors": [{"family": "Petkevicius", "given": "Kasparas", "initials": "K", "orcid": "0000-0003-2295-6065", "researcher": {"href": "https://publications.scilifelab.se/researcher/d807cea22e324d8297776e90d31ed636.json"}}, {"family": "Palmgren", "given": "Henrik", "initials": "H"}, {"family": "Glover", "given": "Matthew S", "initials": "MS"}, {"family": "Ahnmark", "given": "Andrea", "initials": "A"}, {"family": "Andr\u00e9asson", "given": "Anne Christine", "initials": "AC"}, {"family": "Madeyski-Bengtson", "given": "Katja", "initials": "K"}, {"family": "Kawana", "given": "Hiroki", "initials": "H"}, {"family": "Allman", "given": "Erik L", "initials": "EL"}, {"family": "Kaper", "given": "Delaney", "initials": "D", "orcid": "0000-0002-9929-8104", "researcher": {"href": "https://publications.scilifelab.se/researcher/e96d29226c884ec496240844de56499a.json"}}, {"family": "Uhrbom", "given": "Martin", "initials": "M"}, {"family": "Andersson", "given": "Liselotte", "initials": "L"}, {"family": "Aasehaug", "given": "Leif", "initials": "L"}, {"family": "Forsstr\u00f6m", "given": "Johan", "initials": "J"}, {"family": "Wallin", "given": "Simonetta", "initials": "S", "orcid": "0000-0001-5668-1229", "researcher": {"href": "https://publications.scilifelab.se/researcher/bab022f6c191457993878dd9a5983f41.json"}}, {"family": "Ahlstedt", "given": "Ingela", "initials": "I"}, {"family": "Leke", "given": "Renata", "initials": "R"}, {"family": "Karlsson", "given": "Daniel", "initials": "D"}, {"family": "Gonz\u00e1lez-King", "given": "Hern\u00e1n", "initials": "H", "orcid": "0000-0003-4344-9484", "researcher": {"href": "https://publications.scilifelab.se/researcher/58cbb7a64622479f97f2df3e955bed91.json"}}, {"family": "L\u00f6fgren", "given": "Lars", "initials": "L"}, {"family": "Nilsson", "given": "Ralf", "initials": "R"}, {"family": "Pellegrini", "given": "Giovanni", "initials": "G"}, {"family": "Kono", "given": "Nozomu", "initials": "N", "orcid": "0000-0002-0871-8477", "researcher": {"href": "https://publications.scilifelab.se/researcher/ea71ace9343b4d418c78d7cc4bbff16a.json"}}, {"family": "Aoki", "given": "Junken", "initials": "J"}, {"family": "Hess", "given": "Sonja", "initials": "S"}, {"family": "Sienski", "given": "Grzegorz", "initials": "G", "orcid": "0000-0002-2730-7710", "researcher": {"href": "https://publications.scilifelab.se/researcher/f2301dc9b57540e28fa02738caa8f8f3.json"}}, {"family": "Pilon", "given": "Marc", "initials": "M", "orcid": "0000-0003-3919-2882", "researcher": {"href": "https://publications.scilifelab.se/researcher/d45c4ecf9afe463c971af2de53a770a8.json"}}, {"family": "Bohlooly-Y", "given": "Mohammad", "initials": "M"}, {"family": "Maresca", "given": "Marcello", "initials": "M", "orcid": "0000-0003-0796-661X", "researcher": {"href": "https://publications.scilifelab.se/researcher/e3bd1ebf0013464894b127b184a4dca5.json"}}, {"family": "Peng", "given": "Xiao Rong", "initials": "XR"}], "type": "journal-article", "published": "2022-10-14", "journal": {"title": "Nat Commun", "issn": "2041-1723", "volume": "13", "issue": "1", "pages": "6020", "issn-l": "2041-1723"}, "abstract": "The fatty acid composition of phosphatidylethanolamine (PE) determines cellular metabolism, oxidative stress, and inflammation. However, our understanding of how cells regulate PE composition is limited. Here, we identify a genetic locus on mouse chromosome 11, containing two poorly characterized genes Tlcd1 and Tlcd2, that strongly influences PE composition. We generated Tlcd1/2 double-knockout (DKO) mice and found that they have reduced levels of hepatic monounsaturated fatty acid (MUFA)-containing PE species. Mechanistically, TLCD1/2 proteins act cell intrinsically to promote the incorporation of MUFAs into PEs. Furthermore, TLCD1/2 interact with the mitochondria in an evolutionarily conserved manner and regulate mitochondrial PE composition. Lastly, we demonstrate the biological relevance of our findings in dietary models of metabolic disease, where Tlcd1/2 DKO mice display attenuated development of non-alcoholic steatohepatitis compared to controls. Overall, we identify TLCD1/2 proteins as key regulators of cellular PE composition, with our findings having broad implications in understanding and treating disease.", "doi": "10.1038/s41467-022-33735-6", "pmid": "36241646", "labels": {"Swedish Metabolomics Centre": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC9568529"}, {"db": "pii", "key": "10.1038/s41467-022-33735-6"}], "notes": [], "created": "2022-12-05T08:13:47.856Z", "modified": "2025-10-17T13:03:14.568Z"}, {"entity": "publication", "iuid": "6c5dee338d06472182df2147770ff4cc", "links": {"self": {"href": "https://publications.scilifelab.se/publication/6c5dee338d06472182df2147770ff4cc.json"}, "display": {"href": "https://publications.scilifelab.se/publication/6c5dee338d06472182df2147770ff4cc"}}, "title": "A genetic titration of membrane composition in Caenorhabditis elegans reveals its importance for multiple cellular and physiological traits.", "authors": [{"family": "Devkota", "given": "Ranjan", "initials": "R"}, {"family": "Kaper", "given": "Delaney", "initials": "D"}, {"family": "Bodhicharla", "given": "Rakesh", "initials": "R"}, {"family": "Henricsson", "given": "Marcus", "initials": "M"}, {"family": "Bor\u00e9n", "given": "Jan", "initials": "J"}, {"family": "Pilon", "given": "Marc", "initials": "M", "orcid": "0000-0003-3919-2882", "researcher": {"href": "https://publications.scilifelab.se/researcher/d45c4ecf9afe463c971af2de53a770a8.json"}}], "type": "journal article", "published": "2021-08-26", "journal": {"title": "Genetics", "issn": "1943-2631", "volume": "219", "issue": "1", "issn-l": "0016-6731"}, "abstract": "Communicating editor: B. Grant The composition and biophysical properties of cellular membranes must be tightly regulated to maintain the proper functions of myriad processes within cells. To better understand the importance of membrane homeostasis, we assembled a panel of five Caenorhabditis elegans strains that show a wide span of membrane composition and properties, ranging from excessively rich in saturated fatty acids (SFAs) and rigid to excessively rich in polyunsaturated fatty acids (PUFAs) and fluid. The genotypes of the five strain are, from most rigid to most fluid: paqr-1(tm3262); paqr-2(tm3410), paqr-2(tm3410), N2 (wild-type), mdt-15(et14); nhr-49(et8), and mdt-15(et14); nhr-49(et8); acs-13(et54). We confirmed the excess SFA/rigidity-to-excess PUFA/fluidity gradient using the methods of fluorescence recovery after photobleaching (FRAP) and lipidomics analysis. The five strains were then studied for a variety of cellular and physiological traits and found to exhibit defects in: permeability, lipid peroxidation, growth at different temperatures, tolerance to SFA-rich diets, lifespan, brood size, vitellogenin trafficking, oogenesis, and autophagy during starvation. The excessively rigid strains often exhibited defects in opposite directions compared to the excessively fluid strains. We conclude that deviation from wild-type membrane homeostasis is pleiotropically deleterious for numerous cellular/physiological traits. The strains introduced here should prove useful to further study the cellular and physiological consequences of impaired membrane homeostasis.", "doi": "10.1093/genetics/iyab093", "pmid": "34125894", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC9335940"}, {"db": "pii", "key": "6298595"}], "notes": [], "created": "2023-02-16T08:15:40.909Z", "modified": "2023-02-16T08:15:40.926Z"}, {"entity": "publication", "iuid": "0762dde157384547b4115c069024cfd4", "links": {"self": {"href": "https://publications.scilifelab.se/publication/0762dde157384547b4115c069024cfd4.json"}, "display": {"href": "https://publications.scilifelab.se/publication/0762dde157384547b4115c069024cfd4"}}, "title": "Leveraging a gain-of-function allele of Caenorhabditis elegans paqr-1 to elucidate membrane homeostasis by PAQR proteins.", "authors": [{"family": "Busayavalasa", "given": "Kiran", "initials": "K"}, {"family": "Ruiz", "given": "Mario", "initials": "M", "orcid": "0000-0002-7149-6600", "researcher": {"href": "https://publications.scilifelab.se/researcher/35ea5372ccf64bad864d90e4b3698a24.json"}}, {"family": "Devkota", "given": "Ranjan", "initials": "R"}, {"family": "St\u00e5hlman", "given": "Marcus", "initials": "M", "orcid": "0000-0002-4202-0339", "researcher": {"href": "https://publications.scilifelab.se/researcher/01a323cbf0a24269bd32bfc34539e021.json"}}, {"family": "Bodhicharla", "given": "Rakesh", "initials": "R", "orcid": "0000-0002-2344-6318", "researcher": {"href": "https://publications.scilifelab.se/researcher/576a63da68ef49b1a6ff2052398029c3.json"}}, {"family": "Svensk", "given": "Emma", "initials": "E"}, {"family": "Hermansson", "given": "Nils-Olov", "initials": "NO", "orcid": "0000-0003-0170-6649", "researcher": {"href": "https://publications.scilifelab.se/researcher/55f9c6644b354a4891f528786cf81628.json"}}, {"family": "Bor\u00e9n", "given": "Jan", "initials": "J", "orcid": "0000-0003-0786-8091", "researcher": {"href": "https://publications.scilifelab.se/researcher/1e85f6d287ce4c60a7b35b287efb4f79.json"}}, {"family": "Pilon", "given": "Marc", "initials": "M", "orcid": "0000-0003-3919-2882", "researcher": {"href": "https://publications.scilifelab.se/researcher/d45c4ecf9afe463c971af2de53a770a8.json"}}], "type": "journal article", "published": "2020-08-00", "journal": {"title": "PLoS Genet.", "issn": "1553-7404", "volume": "16", "issue": "8", "pages": "e1008975", "issn-l": "1553-7390"}, "abstract": "The C. elegans proteins PAQR-2 (a homolog of the human seven-transmembrane domain AdipoR1 and AdipoR2 proteins) and IGLR-2 (a homolog of the mammalian LRIG proteins characterized by a single transmembrane domain and the presence of immunoglobulin domains and leucine-rich repeats in their extracellular portion) form a complex that protects against plasma membrane rigidification by promoting the expression of fatty acid desaturases and the incorporation of polyunsaturated fatty acids into phospholipids, hence increasing membrane fluidity. In the present study, we leveraged a novel gain-of-function allele of PAQR-1, a PAQR-2 paralog, to carry out structure-function studies. We found that the transmembrane domains of PAQR-2 are responsible for its functional requirement for IGLR-2, that PAQR-1 does not require IGLR-2 but acts via the same pathway as PAQR-2, and that the divergent N-terminal cytoplasmic domains of the PAQR-1 and PAQR-2 proteins serve a regulatory function and may regulate access to the catalytic site of these proteins. We also show that overexpression of human AdipoR1 or AdipoR2 alone is sufficient to confer increased palmitic acid resistance in HEK293 cells, and thus act in a manner analogous to the PAQR-1 gain-of-function allele.", "doi": "10.1371/journal.pgen.1008975", "pmid": "32750056", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC7428288"}, {"db": "pii", "key": "PGENETICS-D-20-00388"}], "notes": [], "created": "2023-02-16T08:05:11.834Z", "modified": "2023-02-16T08:05:11.984Z"}, {"entity": "publication", "iuid": "0ec31b6de15d4b79a1806f6fa3da63ab", "links": {"self": {"href": "https://publications.scilifelab.se/publication/0ec31b6de15d4b79a1806f6fa3da63ab.json"}, "display": {"href": "https://publications.scilifelab.se/publication/0ec31b6de15d4b79a1806f6fa3da63ab"}}, "title": "AdipoR1 and AdipoR2 maintain membrane fluidity in most human cell types and independently of adiponectin.", "authors": [{"family": "Ruiz", "given": "Mario", "initials": "M"}, {"family": "St\u00e5hlman", "given": "Marcus", "initials": "M"}, {"family": "Bor\u00e9n", "given": "Jan", "initials": "J"}, {"family": "Pilon", "given": "Marc", "initials": "M", "orcid": "0000-0003-3919-2882", "researcher": {"href": "https://publications.scilifelab.se/researcher/d45c4ecf9afe463c971af2de53a770a8.json"}}], "type": "journal article", "published": "2019-05-00", "journal": {"title": "J. Lipid Res.", "issn": "1539-7262", "volume": "60", "issue": "5", "pages": "995-1004", "issn-l": "0022-2275"}, "abstract": "The FA composition of phospholipids must be tightly regulated to maintain optimal cell membrane properties and compensate for a highly variable supply of dietary FAs. Previous studies have shown that AdipoR2 and its homologue PAQR-2 are important regulators of phospholipid FA composition in HEK293 cells and Caenorhabditiselegans, respectively. Here we show that both AdipoR1 and AdipoR2 are essential for sustaining desaturase expression and high levels of unsaturated FAs in membrane phospholipids of many human cell types, including primary human umbilical vein endothelial cells, and for preventing membrane rigidification in cells challenged with exogenous palmitate, a saturated FA. Three independent methods confirm the role of the AdipoRs as regulators of membrane composition and fluidity: fluorescence recovery after photobleaching, measurements of Laurdan dye generalized polarization, and mass spectrometry to determine the FA composition of phospholipids. Furthermore, we show that the AdipoRs can prevent lipotoxicity in the complete absence of adiponectin, their putative ligand. We propose that the primary cellular function of AdipoR1 and AdipoR2 is to maintain membrane fluidity in most human cell types and that adiponectin is not required for this function.", "doi": "10.1194/jlr.M092494", "pmid": "30890562", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pii", "key": "S0022-2275(20)32269-0"}, {"db": "pmc", "key": "PMC6495173"}], "notes": [], "created": "2020-01-23T16:12:25.516Z", "modified": "2021-06-21T12:00:27.451Z"}, {"entity": "publication", "iuid": "7f8e9420dba5479c9212fb8fe5cc687e", "links": {"self": {"href": "https://publications.scilifelab.se/publication/7f8e9420dba5479c9212fb8fe5cc687e.json"}, "display": {"href": "https://publications.scilifelab.se/publication/7f8e9420dba5479c9212fb8fe5cc687e"}}, "title": "Membrane fluidity is regulated by the C. elegans transmembrane protein FLD-1 and its human homologs TLCD1/2.", "authors": [{"family": "Ruiz", "given": "Mario", "initials": "M"}, {"family": "Bodhicharla", "given": "Rakesh", "initials": "R"}, {"family": "Svensk", "given": "Emma", "initials": "E"}, {"family": "Devkota", "given": "Ranjan", "initials": "R"}, {"family": "Busayavalasa", "given": "Kiran", "initials": "K"}, {"family": "Palmgren", "given": "Henrik", "initials": "H"}, {"family": "St\u00e5hlman", "given": "Marcus", "initials": "M", "orcid": "0000-0002-4202-0339", "researcher": {"href": "https://publications.scilifelab.se/researcher/01a323cbf0a24269bd32bfc34539e021.json"}}, {"family": "Boren", "given": "Jan", "initials": "J"}, {"family": "Pilon", "given": "Marc", "initials": "M", "orcid": "0000-0003-3919-2882", "researcher": {"href": "https://publications.scilifelab.se/researcher/d45c4ecf9afe463c971af2de53a770a8.json"}}], "type": "journal article", "published": "2018-12-04", "journal": {"volume": "7", "issn": "2050-084X", "issue": null, "pages": null, "title": "Elife", "issn-l": "2050-084X"}, "abstract": "Dietary fatty acids are the main building blocks for cell membranes in animals, and mechanisms must therefore exist that compensate for dietary variations. We isolated C. elegans mutants that improved tolerance to dietary saturated fat in a sensitized genetic background, including eight alleles of the novel gene fld-1 that encodes a homolog of the human TLCD1 and TLCD2 transmembrane proteins. FLD-1 is localized on plasma membranes and acts by limiting the levels of highly membrane-fluidizing long-chain polyunsaturated fatty acid-containing phospholipids. Human TLCD1/2 also regulate membrane fluidity by limiting the levels of polyunsaturated fatty acid-containing membrane phospholipids. FLD-1 and TLCD1/2 do not regulate the synthesis of long-chain polyunsaturated fatty acids but rather limit their incorporation into phospholipids. We conclude that inhibition of FLD-1 or TLCD1/2 prevents lipotoxicity by allowing increased levels of membrane phospholipids that contain fluidizing long-chain polyunsaturated fatty acids.\n\nThis article has been through an editorial process in which the authors decide how to respond to the issues raised during peer review. The Reviewing Editor's assessment is that all the issues have been addressed (see decision letter).", "doi": "10.7554/eLife.40686", "pmid": "30509349", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pii", "key": "40686"}, {"db": "pmc", "key": "PMC6279351"}], "notes": [], "created": "2020-01-23T16:16:17.610Z", "modified": "2021-06-21T13:54:44.388Z"}, {"entity": "publication", "iuid": "7385440a648e4721bdf0bdfa5fa73032", "links": {"self": {"href": "https://publications.scilifelab.se/publication/7385440a648e4721bdf0bdfa5fa73032.json"}, "display": {"href": "https://publications.scilifelab.se/publication/7385440a648e4721bdf0bdfa5fa73032"}}, "title": "Membrane Fluidity Is Regulated Cell Nonautonomously by Caenorhabditiselegans PAQR-2 and Its Mammalian Homolog AdipoR2.", "authors": [{"family": "Bodhicharla", "given": "Rakesh", "initials": "R"}, {"family": "Devkota", "given": "Ranjan", "initials": "R"}, {"family": "Ruiz", "given": "Mario", "initials": "M"}, {"family": "Pilon", "given": "Marc", "initials": "M", "orcid": "0000-0003-3919-2882", "researcher": {"href": "https://publications.scilifelab.se/researcher/d45c4ecf9afe463c971af2de53a770a8.json"}}], "type": "journal article", "published": "2018-09-00", "journal": {"title": "Genetics", "issn": "1943-2631", "volume": "210", "issue": "1", "pages": "189-201", "issn-l": "0016-6731"}, "abstract": "Maintenance of membrane properties is an essential aspect of cellular homeostasis of which the regulatory mechanisms remain mostly uncharacterized. In Caenorhabditis elegans, the PAQR-2 and IGLR-2 proteins act together as a plasma membrane sensor that responds to decreased fluidity by promoting fatty acid desaturation, hence restoring membrane fluidity. Here, we used mosaic analysis for paqr-2 and iglr-2, and tissue-specific paqr-2 expression, to show that membrane homeostasis is achieved cell nonautonomously. Specifically, we found that expression of paqr-2 in the hypodermis, gonad sheath cells, or intestine is sufficient to suppress systemic paqr-2 mutant phenotypes, including tail tip morphology, membrane fluidity in intestinal cells, cold and glucose intolerance, vitellogenin transport to the germline, germ cell development, and brood size. Finally, we show that the cell nonautonomous regulation of membrane homeostasis is conserved in human cells: HEK293 cells that express AdipoR2, a homolog of paqr-2, are able to normalize membrane fluidity in distant cells where AdipoR2 has been silenced. Finally, using C. elegans mutants and small interfering RNA against \u03949 stearoyl-CoA desaturase in HEK293 cells, we show that \u03949 desaturases are essential for the cell nonautonomous maintenance of membrane fluidity. We conclude that cells are able to share membrane components even when they are not in direct contact with each other, and that this contributes to the maintenance of membrane homeostasis in C. elegans and human cells.", "doi": "10.1534/genetics.118.301272", "pmid": "29997234", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pii", "key": "genetics.118.301272"}, {"db": "pmc", "key": "PMC6116961"}], "notes": [], "created": "2020-01-23T16:16:39.298Z", "modified": "2021-06-21T14:08:01.320Z"}, {"entity": "publication", "iuid": "9cbb19e653c646618c1f02621a306881", "links": {"self": {"href": "https://publications.scilifelab.se/publication/9cbb19e653c646618c1f02621a306881.json"}, "display": {"href": "https://publications.scilifelab.se/publication/9cbb19e653c646618c1f02621a306881"}}, "title": "The adiponectin receptor AdipoR2 and its Caenorhabditis elegans homolog PAQR-2 prevent membrane rigidification by exogenous saturated fatty acids.", "authors": [{"family": "Devkota", "given": "Ranjan", "initials": "R"}, {"family": "Svensk", "given": "Emma", "initials": "E"}, {"family": "Ruiz", "given": "Mario", "initials": "M"}, {"family": "St\u00e5hlman", "given": "Marcus", "initials": "M"}, {"family": "Bor\u00e9n", "given": "Jan", "initials": "J", "orcid": "0000-0003-0786-8091", "researcher": {"href": "https://publications.scilifelab.se/researcher/1e85f6d287ce4c60a7b35b287efb4f79.json"}}, {"family": "Pilon", "given": "Marc", "initials": "M", "orcid": "0000-0003-3919-2882", "researcher": {"href": "https://publications.scilifelab.se/researcher/d45c4ecf9afe463c971af2de53a770a8.json"}}], "type": "journal article", "published": "2017-09-00", "journal": {"title": "PLoS Genet.", "issn": "1553-7404", "volume": "13", "issue": "9", "pages": "e1007004", "issn-l": "1553-7390"}, "abstract": "Dietary fatty acids can be incorporated directly into phospholipids. This poses a specific challenge to cellular membranes since their composition, hence properties, could greatly vary with different diets. That vast variations in diets are tolerated therefore implies the existence of regulatory mechanisms that monitor and regulate membrane compositions. Here we show that the adiponectin receptor AdipoR2, and its C. elegans homolog PAQR-2, are essential to counter the membrane rigidifying effects of exogenously provided saturated fatty acids. In particular, we use dietary supplements or mutated E. coli as food, together with direct measurements of membrane fluidity and composition, to show that diets containing a high ratio of saturated to monounsaturated fatty acids cause membrane rigidity and lethality in the paqr-2 mutant. We also show that mammalian cells in which AdipoR2 has been knocked-down by siRNA are unable to prevent the membrane-rigidifying effects of palmitic acid. We conclude that the PAQR-2 and AdipoR2 proteins share an evolutionarily conserved function that maintains membrane fluidity in the presence of exogenous saturated fatty acids.", "doi": "10.1371/journal.pgen.1007004", "pmid": "28886012", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pii", "key": "PGENETICS-D-17-01342"}, {"db": "pmc", "key": "PMC5607217"}], "notes": [], "created": "2020-01-23T16:34:44.458Z", "modified": "2021-06-21T15:29:30.012Z"}]}