{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,4,15]],"date-time":"2025-04-15T11:37:27Z","timestamp":1744717047618,"version":"3.38.0"},"reference-count":46,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,2,16]],"date-time":"2025-02-16T00:00:00Z","timestamp":1739664000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["153318","166168"],"award-info":[{"award-number":["153318","166168"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000156","name":"Fonds de Recherche du Qu\u00e9bec - Sant\u00e9","doi-asserted-by":"publisher","award":["312374","350476"],"award-info":[{"award-number":["312374","350476"]}],"id":[{"id":"10.13039\/501100000156","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Obesity"],"published-print":{"date-parts":[[2025,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Adipose tissue expands through hyperplasia and hypertrophy to store excess lipids, a process that is essential for the maintenance of metabolic homeostasis. The mechanisms regulating adipocyte recruitment from progenitors remain unclear. We have previously identified V\u2010set and transmembrane domain\u2010containing protein 2A (VSTM2A) as a factor promoting fat cell development in vitro. Whether VSTM2A impacts adipose tissue and systemic metabolism in vivo is still unknown.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We generated VSTM2A knockout mice (<jats:italic>Vstm2a<\/jats:italic><jats:sup><jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup>) using clustered regularly interspaced short palindromic repeats (CRISPR)\/CRISPR\u2010associated protein 9 (Cas9) and fed them either a chow or high\u2010fat diet. These mice were evaluated for body weight, adiposity, blood parameters, and glucose homeostasis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p><jats:italic>Vstm2a<\/jats:italic><jats:sup><jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup> mice were viable and showed no body weight differences. Although adipose mass was similar, <jats:italic>Vstm2a<\/jats:italic><jats:sup><jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup> mice had larger adipocytes, an effect linked to inflammation, ectopic lipid deposition, and impaired glucose and lipid metabolism. Transcriptomic analysis revealed that VSTM2A loss affects the expression of several genes in adipose tissue, including some related to the lysosome. Interestingly, acute lysosomal inhibition early in life is sufficient to cause adipocyte hypertrophy in adults.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>VSTM2A is dispensable for adipose tissue formation, but its loss causes adipocyte hypertrophy and impairs glucose and lipid homeostasis. Our study also underscores a critical role of the lysosome in initiating adipogenesis.<\/jats:p><\/jats:sec>","DOI":"10.1002\/oby.24224","type":"journal-article","created":{"date-parts":[[2025,2,17]],"date-time":"2025-02-17T02:31:16Z","timestamp":1739759476000},"page":"522-536","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Loss of <scp>VSTM2A<\/scp> promotes adipocyte hypertrophy and disrupts metabolic homeostasis"],"prefix":"10.1002","volume":"33","author":[{"given":"Manal","family":"Al Dow","sequence":"first","affiliation":[{"name":"Centre de recherche de l'Institut universitaire de cardiologie et de pneumologie de Qu\u00e9bec (CRIUCPQ), Facult\u00e9 de M\u00e9decine Universit\u00e9 Laval  Quebec Qu\u00e9bec City Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Blandine","family":"Secco","sequence":"additional","affiliation":[{"name":"Centre de recherche de l'Institut universitaire de cardiologie et de pneumologie de Qu\u00e9bec (CRIUCPQ), Facult\u00e9 de M\u00e9decine Universit\u00e9 Laval  Quebec Qu\u00e9bec City Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mathilde","family":"Mouchiroud","sequence":"additional","affiliation":[{"name":"Centre de recherche de l'Institut universitaire de cardiologie et de pneumologie de Qu\u00e9bec (CRIUCPQ), Facult\u00e9 de M\u00e9decine Universit\u00e9 Laval  Quebec Qu\u00e9bec City Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marianne","family":"Rochette","sequence":"additional","affiliation":[{"name":"Centre de recherche de l'Institut universitaire de cardiologie et de pneumologie de Qu\u00e9bec (CRIUCPQ), Facult\u00e9 de M\u00e9decine Universit\u00e9 Laval  Quebec Qu\u00e9bec City Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gustavo R.","family":"Gilio","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Sciences, Department of Physiology and Biophysics University of S\u00e3o Paulo  S\u00e3o Paulo Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mickael","family":"Massicard","sequence":"additional","affiliation":[{"name":"Centre de recherche de l'Institut universitaire de cardiologie et de pneumologie de Qu\u00e9bec (CRIUCPQ), Facult\u00e9 de M\u00e9decine Universit\u00e9 Laval  Quebec Qu\u00e9bec City Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marilou","family":"Hardy","sequence":"additional","affiliation":[{"name":"Centre de recherche de l'Institut universitaire de cardiologie et de pneumologie de Qu\u00e9bec (CRIUCPQ), Facult\u00e9 de M\u00e9decine Universit\u00e9 Laval  Quebec Qu\u00e9bec City Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yves","family":"G\u00e9linas","sequence":"additional","affiliation":[{"name":"Centre de recherche de l'Institut universitaire de cardiologie et de pneumologie de Qu\u00e9bec (CRIUCPQ), Facult\u00e9 de M\u00e9decine Universit\u00e9 Laval  Quebec Qu\u00e9bec City Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4769-0806","authenticated-orcid":false,"given":"William T.","family":"Festuccia","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Sciences, Department of Physiology and Biophysics University of S\u00e3o Paulo  S\u00e3o Paulo Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mathieu C.","family":"Morissette","sequence":"additional","affiliation":[{"name":"Centre de recherche de l'Institut universitaire de cardiologie et de pneumologie de Qu\u00e9bec (CRIUCPQ), Facult\u00e9 de M\u00e9decine Universit\u00e9 Laval  Quebec Qu\u00e9bec City Canada"},{"name":"Centre de recherche sur le cancer de l'Universit\u00e9 Laval Universit\u00e9 Laval  Quebec Qu\u00e9bec City Canada"},{"name":"D\u00e9partement de M\u00e9decine, Facult\u00e9 de M\u00e9decine Universit\u00e9 Laval  Quebec Qu\u00e9bec City Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Venkata S. 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