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...