Rapid transformation of white adipocytes into fat-oxidizing machines

Abstract

Adenovirus-induced hyperleptinemia rapidly depletes body fat in normal rats without increasing free fatty acids and ketogenesis, implying that fat-storing adipocytes are oxidizing the fat. To analyze the ultrastructural changes of adipocytes accompanying this functional transformation, we examined the fat tissue by electron microscopy. After 14 days of hyperleptinemia, adipocytes had become shrunken, fatless, and encased in a thick basementmembrane-like matrix. They were crowded with mitochondria that were much smaller than those of brown adipocytes. Their gene expression profile revealed striking up-regulation of peroxisome proliferator-activated receptor ␥ coactivator 1␣ (an up-regulator of mitochondrial biogenesis not normally expressed in white fat), increased uncoupling proteins-1 and -2, and down-regulation of lipogenic enzymes. Phosphorylation of both acetyl CoA carboxylase and AMP-activated protein kinase was increased, thus explaining the increase in fatty acid oxidation. The ability to transform adipocytes into unique fat-burning cells may suggest novel therapeutic strategies for obesity.

Effect of high-fat diet feeding on leptin receptor expression in white adipose tissue in rats: depot- and sex-related differential response

“…Interestingly, the retroperitoneal depot was the one that suffered the greatest increase in weight in both sexes as an effect of HF-diet, and this can be associated with the decrease in OB-Rb mRNA expression levels. Leptin has a direct action on WAT by up-regulating fat oxidation [13] and decreasing lipogenesis [27]. However, we did not find any significant effect of the HF-diet feeding on the expression of the two fat-oxidation related genes studied (PPARa and CPT1).…”

“…[9,10,24,28]. In fact, the role of leptin on white adipose tissue (WAT) has been reported to be essential in modulating the adipocytes' metabolic function [25], up-regulating fat oxidation [13] and decreasing lipogenesis [27]. In this way, it has been postulated that the peripheral effects of leptin, such as in WAT, may also help regulate the entire body weight [7].…”

Augmenting energy expenditure by mitochondrial uncoupling: a role of AMP-activated protein kinase

“…Furthermore, the adipokines leptin and adiponectin (Orci et al 2004;Wu et al 2003) and dietary n-3 PUFA (Kopecky et al 2009) activate AMPK in WAT. It has been found in rodent adipocytes that lipolytic and cAMP-elevating stimuli increase AMPK activity, while its activation by AICAR or phenformin strongly reduces isoproterenol-induced lipolysis and fatty acid release (Daval et al 2005).…”

“…Thus, treatment using leptin (Orci et al 2004), PPARa agonists (Ribet et al 2010), adrenoreceptor agonists and lipolytic agents (Granneman et al 2003;Yehuda-Shnaidman et al 2010), dietary n-3 polyunsaturated fatty acids (Jelenik et al 2010;Kopecky et al 2009;Flachs et al 2005), and thiazolidinediones acting as specific agonists of PPARc [TZD; (Tiraby et al 2003;Wilson-Fritch et al 2004;Petrovic et al 2010)] resulted in reduced adiposity and metabolic disturbances related to obesity, observed mostly under the conditions of high-fat feeding in obesity-prone C57BL/6 mice. Importantly, lipid catabolism in WAT was always up-regulated, and in situ lipogenesis in WAT was suppressed (Orci et al 2004;Ribet et al 2010;Flachs et al 2005;Tiraby et al 2003;Wilson-Fritch et al 2004), suggesting activation of AMPK Genes Nutr (2012) 7:369-386 381 in response to decreased energy status in WAT. Indeed, when studied under the conditions of the above treatments, AMPK in WAT and other tissues was found to be activated (Jelenik et al 2010;Kopecky et al 2009;Orci et al 2004;Ye et al 2006).…”

“…Importantly, lipid catabolism in WAT was always up-regulated, and in situ lipogenesis in WAT was suppressed (Orci et al 2004;Ribet et al 2010;Flachs et al 2005;Tiraby et al 2003;Wilson-Fritch et al 2004), suggesting activation of AMPK Genes Nutr (2012) 7:369-386 381 in response to decreased energy status in WAT. Indeed, when studied under the conditions of the above treatments, AMPK in WAT and other tissues was found to be activated (Jelenik et al 2010;Kopecky et al 2009;Orci et al 2004;Ye et al 2006). Concerning the mechanism of energy expenditure induced by the treatments, mitochondrial uncoupling mediated by UCP1 in WAT adipocytes (Orci et al 2004;Tiraby et al 2003;Petrovic et al 2010;Collins et al 1997;Guerra et al 1998;Himms-Hagen et al 2000) could be involved in most of the cases.…”