10E,12Z-conjugated linoleic acid impairs adipocyte triglyceride storage by enhancing fatty acid oxidation, lipolysis, and mitochondrial reactive oxygen species

Abstract

This article is available online at http://www.jlr.org adverse conditions, such as systemic and adipose tissue infl ammation, insulin resistance, hepatic steatosis, dyslipidemia, and cardiovascular disease ( 3, 4 ). Representing the major cellular constituent of adipose tissue, adipocytes are now regarded as prominent players in the metabolic as well as hormonal regulation of adiposity. In addition to their primary function of energy storage and release, adipocytes secrete a variety of adipokines and lipid factors involved in energy homeostasis, feeding behavior, insulin sensitivity, and infl ammation ( 5, 6 ). Despite the fundamental role adipose tissue plays in whole-body metabolism, nutritive mechanisms that contribute to its maintenance in the context of obesity remain poorly understood.Conjugated linoleic acid (CLA) includes at least 28 naturally occurring isomers of linoleic acid (LA, C18:2), defi ned by conjugated double bonds in different geometric and positional locations. Of these, cis -9, trans -11 (9Z,11E) and trans -10, cis -12 (10E,12Z) CLA are the most abundantly found in the food supply ( 7 ). Based on current evidence that CLA reduces adiposity, several formulations containing equal amounts of the 9Z,11E and 10E,12Z isomers are widely available in supplement form ( 8-10 ). Most evidence attributes the majority of the adiposity-reducing properties to the 10E,12Z-CLA isomer ( 11,12 ), and therefore, Abstract Conjugated linoleic acid (CLA) is a naturally occurring dietary trans fatty acid found in food from ruminant sources. One specifi c CLA isomer, 10E,12Z-CLA, has been associated with health benefi ts, such as reduced adiposity, while simultaneously promoting deleterious effects, such as systemic infl ammation, insulin resistance, and dyslipidemia. The precise mechanisms by which 10E,12Z-CLA exerts these effects remain unknown. Despite potential health consequences, CLA continues to be advertised as a natural weight loss supplement, warranting further studies on its effects on lipid metabolism. We hypothesized that 10E,12Z-CLA impairs lipid storage in adipose tissue by altering the lipid metabolism of white adipocytes. We demonstrate that 10E,12Z-CLA reduced triglyceride storage due to enhanced fatty acid oxidation and lipolysis, coupled with diminished glucose uptake and utilization in cultured adipocytes. This switch to lipid utilization was accompanied by a potent proinfl ammatory response, including the generation of cytokines, monocyte chemotactic factors, and mitochondrial superoxide. Disrupting fatty acid oxidation restored glucose utilization and attenuated the infl ammatory response to 10E,12Z-CLA, suggesting that fatty acid oxidation is critical in promoting this phenotype. With further investigation into the biochemical pathways involved in adipocyte responses to 10E,12Z-CLA, we can discern more information about its safety and effi cacy in promoting weight loss. The prevalence of obesity and associated diseases, such as type 2 diabetes mellitus, is rapidly reaching epidemic proportio...

Trans10, cis12 conjugated linoleic acid increases triacylglycerol accumulation in goat mammary epithelial cells in vitro

“…Previous in vitro research also showed that a relatively low concentration of t10c12-CLA could induce mammary cancer cell apoptosis (Ou et al 2008). In adipocytes, t10c12-CLA inhibited differentiation (Kang et al 2003), and decreased TG storage by reducing glucose uptake, enhancing lipolysis, and increasing the oxidation of fatty acids (den Hartigh et al 2013). Bcl2 expression is able to enhance drug resistance to cell death, whereas Bax, a partner protein of Bcl2, is a promoter of apoptosis, thus the ratio of Bax/Bcl2 is suggested to determine apoptosis (Stoetzer et al 1996).…”

Dietary docosahexaenoic acid reverses nonalcoholic steatohepatitis and fibrosis caused by conjugated linoleic acid supplementation in mice

“…We observed a CLA-induced reduction of AT mass was accompanied by hepatomegaly with steatosis. CLA has been shown to decrease TG content in AT by increasing lipolysis caused by the differential expression and localisation of lipid droplet-associated proteins such as perilipin (lipolysis modulation) and adipose differentiation-related protein (lipid storage) (Chung, Brown, Sandberg, & McIntosh, 2005;den Hartigh, Han, Wang, Omer, & Chait, 2013). A decrease in the expression of perilipin, the outer surface lipid droplet protein that serves to protect lipids from hydrolysis by lipases in AT, would increase basal lipolytic activity and decrease fat mass (Tansey et al, 2001).…”

Trans-10,cis-12-conjugated linoleic acid worsens renal pathology and alters cyclooxygenase derived oxylipins in obesity-associated nephropathy

“…This finding therefore has potential significance to human health, because it is this population that is targeted by aggressive marketing of CLA as a weight lowering product, and the available supplements contain both isomers. The t10,c12 CLA isomer is generally believed to be the most active in reducing adipose mass [29][30][31][32]. In these older fa/fa Zucker rats, neither CLA isomer reduced body weight or epididymal fat mass [16].…”

“…We also have shown that t10,c12 CLA decreases adipocyte dysfunction by reducing cell size and increasing cell number in epididymal adipose tissue of fa/fa Zucker rats [16,28], and it is generally believed that t10,c12 CLA is responsible for effects on body composition [29][30][31][32]. Animal models of inflammation and obesity have shown that a mixture of CLA isomers increases antiinflammatory cytokines and decreases proinflammatory cytokines [33][34][35][36].…”