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These abnormalities cause loss of white ATs, whitening followed by loss of brown ATs, and impaired \u201cbrowning\u201d of white ATs. Consequently, mice exhibit compromised thermogenic capacity and develop dyslipidemia, hepatic steatosis, insulin resistance, and type 2 diabetes. While these effects of PIK3C3 largely contrast previous findings with the autophagy-related (ATG) protein ATG7 in adipocytes, mice with a combined deficiency in both factors reveal a dominant role of the PIK3C3-deficient phenotype. We have also found that dietary lipid excess exacerbates AT pathologies caused by PIK3C3 deficiency. Surprisingly, glucose tolerance is spared in adipocyte-specific PIK3C3-deficient mice, a phenotype that is more evident during dietary lipid excess. These findings reveal a crucial yet complex role for PIK3C3 in ATs, with potential therapeutic implications.<\/jats:p>","DOI":"10.1073\/pnas.2214874120","type":"journal-article","created":{"date-parts":[[2022,12,27]],"date-time":"2022-12-27T16:25:01Z","timestamp":1672158301000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":22,"title":["Lipid kinase PIK3C3 maintains healthy brown and white adipose tissues to prevent metabolic diseases"],"prefix":"10.1073","volume":"120","author":[{"given":"Wenqiang","family":"Song","sequence":"first","affiliation":[{"name":"Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. 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