An obesogenic diet impairs uncoupled substrate oxidation and promotes whitening of the brown adipose tissue in rats.

Brown adipose tissue (BAT) is rich in mitochondria containing uncoupling protein 1 (UCP1) and dissipates energy through thermogenesis. However, even though BAT mass and its UCP1 content increase in rodents chronically fed a high-fat sucrose-enriched diet (HFS), marked expansion of adiposity still occurs in these animals, suggesting insufficient BAT-mediated HFS diet-induced thermogenesis. Thus, the objective of this study was to investigate the metabolic and molecular mechanisms that regulate BAT thermogenesis in HFS-induced obesity. To accomplish this, rats were fed either a standard chow or HFS for 8 weeks. Subsequently, glucose and fatty acid metabolism and the molecular mechanisms underlying these processes were assessed in freshly isolated primary BAT adipocytes. Despite increasing BAT mass and its UCP1 content, HFS reduced glucose and palmitate oxidation in BAT adipocytes. It also markedly diminished tyrosine hydroxylase content and lipolysis in these cells. Conversely, glucose uptake, lactate production, glycerol incorporation into lipids, palmitate incorporation into triacylglycerol (TAG), phosphoenolpyruvate carboxykinase and glycerol kinase levels, and lipoprotein lipase and cluster of differentiation 36 gene expression were increased. In summary, HFS enhanced glyceroneogenesis and shifted BAT metabolism toward TAG synthesis by impairing UCP1-mediated substrate oxidation and by enhancing fatty acid esterification in intact brown adipocytes. These adaptive metabolic responses to chronic HFS feeding attenuated BAT thermogenic capacity and favored the development of obesity. Abstract figure legend In brown adipocytes from lean rats fed a SC diet, glucose and fatty acids (FA) were diverted essentially toward uncoupling protein 1 (UCP1)-mediated substrate oxidation and thermogenesis. Conversely, in BAT of rats fed a HFS obesogenic diet, despite increases in UCP1, carnitine palmitoyltransferase 1B (CPT1B), and peroxisome proliferator-activated receptor γ coactivator 1α (PGC1α) contents, substrate metabolism in BAT adipocytes was shifted toward triacylglycerol (TAG) synthesis/storage. This was characterized by reduced UCP1-mediated glucose and fatty acid oxidation. These adaptive responses to chronic HFS were supported by increased contents of phosphoenolpyruvate carboxykinase (PEPCK) and glycerol kinase (GyK). This article is protected by copyright. All rights reserved.