{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T18:47:11Z","timestamp":1792176431666,"version":"4.4.0"},"reference-count":31,"publisher":"Oxford University Press (OUP)","issue":"21","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,10,13]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Hypertriglyceridemia is a major risk factor for cardiometabolic diseases. VPS13C is a genome-wide significant locus for triglyceride with an incomplete understanding of its functional role in triglyceride biology. In this study, we investigated the transcriptomic associations and functional roles of VPS13C in triglyceride metabolism.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We analyzed VPS13C expression in subcutaneous adipose tissue and assessed fasting serum lipid levels (including total cholesterol and triglycerides) in participants from the Africa America Diabetes Mellitus (AADM) study. In parallel, we conducted functional studies in 3T3-L1 mouse adipocytes, where Vps13c was knocked down using siRNA. We then evaluated markers of adipogenesis, lipogenesis, and triglyceride metabolism.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In human subjects, VPS13C expression in subcutaneous adipose tissue was inversely associated with fasting triglyceride levels but showed non-significant correlation with total cholesterol. In 3T3-L1 cells, Vps13c knockdown impaired adipocyte differentiation, evidenced by reduced lipid droplet formation and lower intracellular levels of triglycerides, glycerol, and fatty acids. This knockdown also led to significant downregulation of Pparg expression and suppression of PPAR\u03b3-mediated pathways, as well as genes involved in adipogenesis and lipogenesis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>VPS13C is associated with circulating triglyceride levels and plays a critical role in adipocyte differentiation, adipogenesis and lipogenesis. These findings suggest that VPS13C may play an important role in triglyceride-related metabolic disorders.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/hmg\/ddag108","type":"journal-article","created":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T11:37:45Z","timestamp":1791027465000},"source":"Crossref","is-referenced-by-count":0,"title":["VPS13C regulates triglyceride homeostasis and adipocyte differentiation"],"prefix":"10.1093","volume":"35","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4879-065X","authenticated-orcid":false,"given":"Antwi-Boasiako","family":"Oteng","sequence":"first","affiliation":[{"name":"Center for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health , 12 South Drive, Bethesda, MD , 20892,","place":["United States"]},{"name":"Department of Integrative Genomics and Epidemiology, School of Graduate Studies, Meharry Medical College , 1023 21st Ave. North, Nashville, TN , 37208,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayo P","family":"Doumatey","sequence":"additional","affiliation":[{"name":"Center for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health , 12 South Drive, Bethesda, MD , 20892,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashton F","family":"Oliver","sequence":"additional","affiliation":[{"name":"Department of Integrative Genomics and Epidemiology, School of Graduate Studies, Meharry Medical College , 1023 21st Ave. North, Nashville, TN , 37208,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karlijn A C","family":"Meeks","sequence":"additional","affiliation":[{"name":"Center for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health , 12 South Drive, Bethesda, MD , 20892,","place":["United States"]},{"name":"Division of Endocrinology, Diabetes and Nutrition, Department of Medicine, University of Maryland School of Medicine , 670 W. Baltimore Street, Baltimore, MD , 21201,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Lei","sequence":"additional","affiliation":[{"name":"Center for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health , 12 South Drive, Bethesda, MD , 20892,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabeth F","family":"Heuston","sequence":"additional","affiliation":[{"name":"Center for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health , 12 South Drive, Bethesda, MD , 20892,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Binta","family":"Jalloh","sequence":"additional","affiliation":[{"name":"Center for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health , 12 South Drive, Bethesda, MD , 20892,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bayu","family":"Sisay","sequence":"additional","affiliation":[{"name":"Microarrays and Single Cell Genomics Core, National Human Genome Research Institute, National Institutes of Health , 49 Convent Drive, Bethesda, MD , 20892,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdel","family":"Elkahloun","sequence":"additional","affiliation":[{"name":"Microarrays and Single Cell Genomics Core, National Human Genome Research Institute, National Institutes of Health , 49 Convent Drive, Bethesda, MD , 20892,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adebowale A","family":"Adeyemo","sequence":"additional","affiliation":[{"name":"Center for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health , 12 South Drive, Bethesda, MD , 20892,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles N","family":"Rotimi","sequence":"additional","affiliation":[{"name":"Center for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health , 12 South Drive, Bethesda, MD , 20892,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,10,16]]},"reference":[{"key":"2026101614000088600_ref1","doi-asserted-by":"publisher","first-page":"1856","DOI":"10.1038\/s42255-024-01106-8","article-title":"On the pathogenesis of obesity: causal models and missing pieces of the puzzle","volume":"6","author":"Magkos","year":"2024","journal-title":"Nat Metab"},{"key":"2026101614000088600_ref2","doi-asserted-by":"publisher","first-page":"4677","DOI":"10.1038\/s41598-018-22962-x","article-title":"Abdominal subcutaneous and visceral adipocyte size, lipolysis and inflammation relate to insulin resistance in male obese humans","volume":"8","author":"Verboven","year":"2018","journal-title":"Sci Rep"},{"key":"2026101614000088600_ref3","doi-asserted-by":"publisher","DOI":"10.1016\/j.obpill.2024.100108","article-title":"Obesity, dyslipidemia, and cardiovascular disease: a joint expert review from the obesity medicine association and the National Lipid Association 2024","volume":"10","author":"Bays","year":"2024","journal-title":"Obes Pillars"},{"key":"2026101614000088600_ref4","doi-asserted-by":"publisher","first-page":"626","DOI":"10.1016\/S0140-6736(14)61177-6","article-title":"Triglycerides and cardiovascular disease","volume":"384","author":"Nordestgaard","year":"2014","journal-title":"Lancet"},{"key":"2026101614000088600_ref5","doi-asserted-by":"publisher","first-page":"483","DOI":"10.1016\/j.atherosclerosis.2015.01.039","article-title":"New insights into the pathophysiology of dyslipidemia in type 2 diabetes","volume":"239","author":"Taskinen","year":"2015","journal-title":"Atherosclerosis"},{"key":"2026101614000088600_ref6","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2023.104548","article-title":"Ancestral and environmental patterns in the association between triglycerides and other cardiometabolic risk factors","volume":"91","author":"Meeks","year":"2023","journal-title":"EBioMedicine"},{"key":"2026101614000088600_ref7","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0223189","article-title":"Dyslipidemias and cardiovascular risk scores in urban and rural populations in north-western Tanzania and southern Uganda","volume":"14","author":"Kavishe","year":"2019","journal-title":"PLoS One"},{"key":"2026101614000088600_ref8","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0243103","article-title":"Prevalence of dyslipidemia and associated risk factors among adult residents of Mekelle City, Northern Ethiopia","volume":"16","author":"Gebreegziabiher","year":"2021","journal-title":"PLoS One"},{"key":"2026101614000088600_ref9","doi-asserted-by":"publisher","first-page":"425","DOI":"10.1083\/jcb.201606078","article-title":"The Vps13p-Cdc31p complex is directly required for TGN late endosome transport and TGN homotypic fusion","volume":"216","author":"De","year":"2017","journal-title":"J Cell Biol"},{"key":"2026101614000088600_ref10","doi-asserted-by":"publisher","first-page":"728","DOI":"10.1159\/000354475","article-title":"Chorein sensitivity of actin polymerization, cell shape and mechanical stiffness of vascular endothelial cells","volume":"32","author":"Alesutan","year":"2013","journal-title":"Cell Physiol Biochem"},{"key":"2026101614000088600_ref11","doi-asserted-by":"publisher","first-page":"2066","DOI":"10.1159\/000479901","article-title":"Lithium sensitivity of store operated Ca2+ entry and survival of fibroblasts isolated from chorea-Acanthocytosis patients","volume":"42","author":"Pelzl","year":"2017","journal-title":"Cell Physiol Biochem"},{"key":"2026101614000088600_ref12","doi-asserted-by":"publisher","first-page":"500","DOI":"10.1016\/j.ajhg.2016.01.014","article-title":"Loss of VPS13C function in autosomal-recessive parkinsonism causes mitochondrial dysfunction and increases PINK1\/parkin-dependent Mitophagy","volume":"98","author":"Lesage","year":"2016","journal-title":"Am J Hum Genet"},{"key":"2026101614000088600_ref13","doi-asserted-by":"publisher","first-page":"918","DOI":"10.1080\/15548627.2015.1034413","article-title":"TipC and the chorea-acanthocytosis protein VPS13A regulate autophagy in Dictyostelium and human HeLa cells","volume":"11","author":"Munoz-Braceras","year":"2015","journal-title":"Autophagy"},{"key":"2026101614000088600_ref14","doi-asserted-by":"publisher","first-page":"1359","DOI":"10.1086\/375454","article-title":"Cohen syndrome is caused by mutations in a novel gene, COH1, encoding a transmembrane protein with a presumed role in vesicle-mediated sorting and intracellular protein transport","volume":"72","author":"Kolehmainen","year":"2003","journal-title":"Am J Hum Genet"},{"key":"2026101614000088600_ref15","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1038\/88825","article-title":"The gene encoding a newly discovered protein, chorein, is mutated in chorea-acanthocytosis","volume":"28","author":"Ueno","year":"2001","journal-title":"Nat Genet"},{"key":"2026101614000088600_ref16","doi-asserted-by":"publisher","DOI":"10.1177\/25152564221125613","article-title":"VPS13A and VPS13C influence lipid droplet abundance. Contact: the journal of inter-organelle","volume":"5","author":"Chen","year":"2022","journal-title":"Communication"},{"key":"2026101614000088600_ref17","doi-asserted-by":"publisher","first-page":"3625","DOI":"10.1083\/jcb.201807019","article-title":"VPS13A and VPS13C are lipid transport proteins differentially localized at ER contact sites","volume":"217","author":"Kumar","year":"2018","journal-title":"J Cell Biol"},{"key":"2026101614000088600_ref18","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1016\/j.molmet.2017.10.014","article-title":"Vacuolar protein sorting 13C is a novel lipid droplet protein that inhibits lipolysis in brown adipocytes","volume":"7","author":"Ramseyer","year":"2018","journal-title":"Mol Metab"},{"key":"2026101614000088600_ref19","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines11041132","article-title":"Uncoupling lipid synthesis from adipocyte development","volume":"11","author":"Wan","year":"2023","journal-title":"Biomedicines"},{"key":"2026101614000088600_ref20","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1016\/S0014-2999(02)01431-0","article-title":"Peroxisome proliferator activated receptors and obesity","volume":"440","author":"Kersten","year":"2002","journal-title":"Eur J Pharmacol"},{"key":"2026101614000088600_ref21","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1016\/j.tem.2014.04.001","article-title":"PPARgamma and the global map of adipogenesis and beyond","volume":"25","author":"Lefterova","year":"2014","journal-title":"Trends Endocrinol Metab"},{"key":"2026101614000088600_ref22","doi-asserted-by":"publisher","first-page":"17119","DOI":"10.1074\/jbc.RA118.003608","article-title":"The TEA domain family transcription factor TEAD4 represses murine adipogenesis by recruiting the cofactors VGLL4 and CtBP2 into a transcriptional complex","volume":"293","author":"Zhang","year":"2018","journal-title":"J Biol Chem"},{"key":"2026101614000088600_ref23","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1016\/j.metabol.2019.03.003","article-title":"Systemic PPARgamma deletion in mice provokes lipoatrophy, organomegaly, severe type 2 diabetes and metabolic inflexibility","volume":"95","author":"Gilardi","year":"2019","journal-title":"Metabolism"},{"key":"2026101614000088600_ref24","doi-asserted-by":"publisher","first-page":"18656","DOI":"10.1073\/pnas.1314863110","article-title":"Lipoatrophy and severe metabolic disturbance in mice with fat-specific deletion of PPAR\u03b3","volume":"110","author":"Wang","year":"2013","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2026101614000088600_ref25","doi-asserted-by":"publisher","first-page":"11373","DOI":"10.1073\/pnas.0306743102","article-title":"Deletion of PPAR in adipose tissues of mice protects against high fat diet-induced obesity andinsulin resistance","volume":"102","author":"Jones","year":"2005","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2026101614000088600_ref26","doi-asserted-by":"publisher","first-page":"611","DOI":"10.1016\/S1097-2765(00)80211-7","article-title":"PPAR\u03b3 is required for the differentiation of adipose tissue In vivo and In vitro","volume":"4","author":"Rosen","year":"1999","journal-title":"Mol Cell"},{"key":"2026101614000088600_ref27","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1016\/S1047-2797(00)00180-0","article-title":"Search of susceptibility genes for type 2 diabetes in West Africa: the design and results of the first phase of the AADM study","volume":"11","author":"Rotimi","year":"2001","journal-title":"Ann Epidemiol"},{"key":"2026101614000088600_ref28","doi-asserted-by":"publisher","first-page":"838","DOI":"10.2337\/diabetes.53.3.838","article-title":"A genome-wide search for type 2 diabetes susceptibility genes in west Africans : the Africa America diabetes mellitus (AADM) study","volume":"53","author":"Rotimi","year":"2004","journal-title":"Diabetes"},{"key":"2026101614000088600_ref29","doi-asserted-by":"publisher","first-page":"3195","DOI":"10.1038\/s41467-019-10967-7","article-title":"ZRANB3 is an African-specific type 2 diabetes locus associated with beta-cell mass and insulin response","volume":"10","author":"Adeyemo","year":"2019","journal-title":"Nat Commun"},{"key":"2026101614000088600_ref30","doi-asserted-by":"publisher","first-page":"421","DOI":"10.1093\/bioinformatics\/bty648","article-title":"Scaling read aligners to hundreds of threads on general-purpose processors","volume":"35","author":"Langmead","year":"2019","journal-title":"Bioinformatics"},{"key":"2026101614000088600_ref31","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-12-323","article-title":"RSEM: accurate transcript quantification from RNA-Seq data with or without a reference genome","volume":"12","author":"Li","year":"2011","journal-title":"BMC Bioinformatics"}],"container-title":["Human Molecular Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/hmg\/article-pdf\/35\/21\/ddag108\/72051201\/ddag108.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/hmg\/article-pdf\/35\/21\/ddag108\/72051201\/ddag108.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T18:00:07Z","timestamp":1792173607000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/hmg\/article\/doi\/10.1093\/hmg\/ddag108\/8931685"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026]]},"references-count":31,"journal-issue":{"issue":"21","published-print":{"date-parts":[[2026,10,13]]}},"URL":"https:\/\/doi.org\/10.1093\/hmg\/ddag108","relation":{},"ISSN":["0964-6906","1460-2083"],"issn-type":[{"value":"0964-6906","type":"print"},{"value":"1460-2083","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026]]},"published":{"date-parts":[[2026]]},"article-number":"ddag108"}}