{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T04:30:47Z","timestamp":1761539447848},"reference-count":47,"publisher":"The Endocrine Society","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2010,5,1]]},"abstract":"<jats:p>Lipodystrophy with high nonesterified fatty acid (FA) efflux is reported in humans receiving highly active antiretroviral therapy (HAART) to treat HIV infection. Ritonavir, a common component of HAART, alters adipocyte FA efflux, but the mechanism for this effect is not established. To investigate ritonavir-induced changes in FA flux and recycling through acylglycerols, we exposed differentiated murine 3T3-L1 adipocytes to ritonavir for 14 d. FA efflux, uptake, and incorporation into acylglycerols were measured. To identify a mediator of FA efflux, we measured adipocyte triacylglycerol lipase (ATGL) transcript and protein. To determine whether ritonavir-treated adipocytes increased glycerol backbone synthesis for FA reesterification, we measured labeled glycerol and pyruvate incorporation into triacylglycerol (TAG). Ritonavir-treated cells had increased FA efflux, uptake, and incorporation into TAG (all P &amp;lt; 0.01). Ritonavir increased FA efflux without consistently increasing glycerol release or changing TAG mass, suggesting increased partial TAG hydrolysis. Ritonavir-treated adipocytes expressed significantly more ATGL mRNA (P &amp;lt; 0.05) and protein (P &amp;lt; 0.05). Ritonavir increased glycerol (P &amp;lt; 0.01) but not pyruvate (P = 0.41), utilization for TAG backbone synthesis. Consistent with this substrate utilization, glycerol kinase transcript (required for glycerol incorporation into TAG backbone) was up-regulated (P &amp;lt; 0.01), whereas phosphoenolpyruvate carboxykinase transcript (required for pyruvate utilization) was down-regulated (P &amp;lt; 0.001). In 3T3-L1 adipocytes, long-term ritonavir exposure perturbs FA metabolism by increasing ATGL-mediated partial TAG hydrolysis, thus increasing FA efflux, and leads to compensatory increases in FA reesterification with glycerol and acylglycerols. These changes in FA metabolism may, in part, explain the increased FA efflux observed in ritonavir-associated lipodystrophy.<\/jats:p>","DOI":"10.1210\/en.2009-1364","type":"journal-article","created":{"date-parts":[[2010,3,13]],"date-time":"2010-03-13T02:09:41Z","timestamp":1268446181000},"page":"2097-2105","source":"Crossref","is-referenced-by-count":9,"title":["Long-Term Ritonavir Exposure Increases Fatty Acid and Glycerol Recycling in 3T3-L1 Adipocytes as Compensatory Mechanisms for Increased Triacylglycerol Hydrolysis"],"prefix":"10.1210","volume":"151","author":[{"given":"Diane C.","family":"Adler-Wailes","sequence":"first","affiliation":[{"name":"Unit on Growth and Obesity (D.C.A.-W., E.L.G., J.A.Y.), Program in Developmental Endocrinology and Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services, Washington University School of Medicine, St. Louis, Missouri 63110"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Evan L.","family":"Guiney","sequence":"first","affiliation":[{"name":"Unit on Growth and Obesity (D.C.A.-W., E.L.G., J.A.Y.), Program in Developmental Endocrinology and Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services, Washington University School of Medicine, St. Louis, Missouri 63110"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nathan E.","family":"Wolins","sequence":"first","affiliation":[{"name":"Division of Nutritional Science (N.E.W.), Washington University School of Medicine, St. Louis, Missouri 63110"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jack A.","family":"Yanovski","sequence":"first","affiliation":[{"name":"Unit on Growth and Obesity (D.C.A.-W., E.L.G., J.A.Y.), Program in Developmental Endocrinology and Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services, Washington University School of Medicine, St. Louis, Missouri 63110"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"80","published-online":{"date-parts":[[2010,3,12]]},"reference":[{"key":"2020071613112084600_R1","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.biochi.2004.12.005","article-title":"Proposed involvement of adipocyte glyceroneogenesis and phosphoenolpyruvate carboxykinase in the metabolic syndrome.","volume":"87","author":"Cadoudal","year":"2005","journal-title":"Biochimie (Paris)"},{"key":"2020071613112084600_R2","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1210\/er.2008-0007","article-title":"Glycerolipid metabolism and signaling in health and disease.","volume":"29","author":"Prentki","year":"2008","journal-title":"Endocr 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