{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T20:24:02Z","timestamp":1777580642285,"version":"3.51.4"},"reference-count":43,"publisher":"The Endocrine Society","issue":"9","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2016,9,1]]},"abstract":"<jats:p>Obesity is one of the major risk factors for the development of cardiovascular diseases and is characterized by abnormal accumulation of adipose tissue, including perivascular adipose tissue (PVAT). However, brown adipose tissue (BAT) activation reduces visceral adiposity. To demonstrate that severe brown fat lipoatrophy might accelerate atherosclerotic process, we generated a new mouse model without insulin receptor (IR) in BAT and without apolipoprotein (Apo)E (BAT-specific IR knockout [BATIRKO];ApoE\u2212\/\u2212 mice) and assessed vascular and metabolic alterations associated to obesity. In addition, we analyzed the contribution of the adipose organ to vascular inflammation. Brown fat lipoatrophy induces visceral adiposity, mainly in gonadal depot (gonadal white adipose tissue [gWAT]), severe glucose intolerance, high postprandial glucose levels, and a severe defect in acute insulin secretion. BATIRKO;ApoE\u2212\/\u2212 mice showed greater hypertriglyceridemia than the obtained in ApoE\u2212\/\u2212 and hypercholesterolemia similar to ApoE\u2212\/\u2212 mice. BATIRKO;ApoE\u2212\/\u2212 mice, in addition to primary insulin resistance in BAT, also showed a significant decrease in insulin signaling in liver, gWAT, heart, aorta artery, and thoracic PVAT. More importantly, our results suggest that severe brown fat lipoatrophy aggravates the atherosclerotic process, characterized by a significant increase of lipid depots, atherosclerotic coverage, lesion size and complexity, increased macrophage infiltration, and proinflammatory markers expression. Finally, an increase of TNF-\u03b1 and leptin as well as a decrease of adiponectin by BAT, gWAT, and thoracic PVAT might also be responsible of vascular damage. Our results suggest that severe brown lipoatrophy aggravates atherosclerotic process. Thus, BAT activation might protect against obesity and its associated metabolic alterations.<\/jats:p>","DOI":"10.1210\/en.2016-1148","type":"journal-article","created":{"date-parts":[[2016,7,14]],"date-time":"2016-07-14T17:37:21Z","timestamp":1468517841000},"page":"3517-3528","source":"Crossref","is-referenced-by-count":18,"title":["Severe Brown Fat Lipoatrophy Aggravates Atherosclerotic Process in Male Mice"],"prefix":"10.1210","volume":"157","author":[{"given":"Almudena","family":"G\u00f3mez-Hern\u00e1ndez","sequence":"first","affiliation":[{"name":"Biochemistry and Molecular Biology II Department, School of Pharmacy, Complutense University of Madrid; Health Research Institute of San Carlos Clinic Hospital; and Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Diabetes y Enfermedades Metab\u00f3licas Asociadas 28020 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nuria","family":"Beneit","sequence":"first","affiliation":[{"name":"Biochemistry and Molecular Biology II Department, School of Pharmacy, Complutense University of Madrid; 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