{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T08:01:03Z","timestamp":1790928063254,"version":"4.1.0"},"reference-count":91,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2021,12,21]],"date-time":"2021-12-21T00:00:00Z","timestamp":1640044800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["1R01DK121797-01A1"],"award-info":[{"award-number":["1R01DK121797-01A1"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["1R01DK126884-01A1"],"award-info":[{"award-number":["1R01DK126884-01A1"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart Lung and Blood Institute","doi-asserted-by":"publisher","award":["K01HL-125445"],"award-info":[{"award-number":["K01HL-125445"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart Lung and Blood Institute","doi-asserted-by":"publisher","award":["P01 HL05197-11"],"award-info":[{"award-number":["P01 HL05197-11"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["P20GM104357-02"],"award-info":[{"award-number":["P20GM104357-02"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Institute of Health","award":["P30 GM127211"],"award-info":[{"award-number":["P30 GM127211"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>The nuclear receptor PPAR\u03b1 is associated with reducing adiposity, especially in the liver, where it transactivates genes for \u03b2-oxidation. Contrarily, the function of PPAR\u03b1 in extrahepatic tissues is less known. Therefore, we established the first adipose-specific PPAR\u03b1 knockout (PparaFatKO) mice to determine the signaling position of PPAR\u03b1 in adipose tissue expansion that occurs during the development of obesity. To assess the function of PPAR\u03b1 in adiposity, female and male mice were placed on a high-fat diet (HFD) or normal chow for 30 weeks. Only the male PparaFatKO animals had significantly more adiposity in the inguinal white adipose tissue (iWAT) and brown adipose tissue (BAT) with HFD, compared to control littermates. No changes in adiposity were observed in female mice compared to control littermates. In the males, the loss of PPAR\u03b1 signaling in adipocytes caused significantly higher cholesterol esters, activation of the transcription factor sterol regulatory element-binding protein-1 (SREBP-1), and a shift in macrophage polarity from M2 to M1 macrophages. We found that the loss of adipocyte PPAR\u03b1 caused significantly higher expression of the Per-Arnt-Sim kinase (PASK), a kinase that activates SREBP-1. The hyperactivity of the PASK\u2013SREBP-1 axis significantly increased the lipogenesis proteins fatty acid synthase (FAS) and stearoyl-Coenzyme A desaturase 1 (SCD1) and raised the expression of genes for cholesterol metabolism (Scarb1, Abcg1, and Abca1). The loss of adipocyte PPAR\u03b1 increased Nos2 in the males, an M1 macrophage marker indicating that the population of macrophages had changed to proinflammatory. Our results demonstrate the first adipose-specific actions for PPAR\u03b1 in protecting against lipogenesis, inflammation, and cholesterol ester accumulation that leads to adipocyte tissue expansion in obesity.<\/jats:p>","DOI":"10.3390\/cells11010004","type":"journal-article","created":{"date-parts":[[2021,12,21]],"date-time":"2021-12-21T09:50:43Z","timestamp":1640080243000},"page":"4","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":74,"title":["Adipose-Specific PPAR\u03b1 Knockout Mice Have Increased Lipogenesis by PASK\u2013SREBP1 Signaling and a Polarity Shift to Inflammatory Macrophages in White Adipose Tissue"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7599-1529","authenticated-orcid":false,"suffix":"Jr.","given":"Terry D.","family":"Hinds","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Nutritional Sciences, University of Kentucky, Lexington, KY 40508, USA"},{"name":"Barnstable Brown Diabetes Center, University of Kentucky, Lexington, KY 40508, USA"},{"name":"Markey Cancer Center, University of Kentucky, Lexington, KY 40508, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zachary A.","family":"Kipp","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Nutritional Sciences, University of Kentucky, Lexington, KY 40508, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mei","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Nutritional Sciences, University of Kentucky, Lexington, KY 40508, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederique B.","family":"Yiannikouris","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Nutritional Sciences, University of Kentucky, Lexington, KY 40508, USA"},{"name":"Barnstable Brown Diabetes Center, University of Kentucky, Lexington, KY 40508, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1910-4865","authenticated-orcid":false,"given":"Andrew J.","family":"Morris","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, College of Medicine, University of Kentucky, Lexington, KY 40508, USA"},{"name":"Lexington Veterans Affairs Medical Center, Lexington, KY 40508, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donald F.","family":"Stec","sequence":"additional","affiliation":[{"name":"Small Molecule NMR Facility Core, Vanderbilt Institute of Chemical Biology, Vanderbilt University, Nashville, TN 37235, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5966-9089","authenticated-orcid":false,"given":"Walter","family":"Wahli","sequence":"additional","affiliation":[{"name":"Lee Kong Chian School of Medicine, Nanyang Technological University Singapore, Clinical Sciences Building, Singapore 308232, Singapore"},{"name":"Toxalim Research Center in Food Toxicology (UMR 1331), INRAE, ENVT, INP\u2014PURPAN, UPS, Universit\u00e9 de Toulouse, F-31300 Toulouse, France"},{"name":"Center for Integrative Genomics, Universit\u00e9 de Lausanne, Le G\u00e9nopode, CH-1015 Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8359-4008","authenticated-orcid":false,"given":"David E.","family":"Stec","sequence":"additional","affiliation":[{"name":"Department of Physiology & Biophysics, Cardiorenal and Metabolic Diseases Research Center, University of Mississippi Medical Center, Jackson, MS 39216, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1038\/347645a0","article-title":"Activation of a member of the steroid hormone receptor superfamily by peroxisome proliferators","volume":"347","author":"Issemann","year":"1990","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"9804","DOI":"10.1074\/jbc.RA120.013700","article-title":"Bilirubin remodels murine white adipose tissue by reshaping mitochondrial activity and the coregulator profile of peroxisome proliferator-activated receptor alpha","volume":"295","author":"Gordon","year":"2020","journal-title":"J. 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