Conjugated Linoleic Acid Induces Uncoupling Protein 1 in White Adipose Tissue of ob/ob Mice

Conjugated linoleic acid (CLA) reduces body weight and adipose mass in a variety of species. The mechanisms by which CLA depletes adipose mass are unclear, but two independent microarray analyses indicate that in white adipose tissue (WAT), uncoupling protein 1 (UCP1) was among genes most changed by CLA. The objective of this study was to determine whether CLA induces ectopic expression of UCP1 in WAT, which may contribute to increased energy expenditure and weight loss. Six-week old, male ob/ob mice were fed either a control diet (CON) or a diet supplemented with 1.5% mixed isomer CLA (CLA) for 4 weeks. A third group of mice (LEPTIN) was fed the control diet and received daily injections of recombinant leptin as a positive control for adipose depletion in ob/ob mice. CLA did not alter several mRNA markers of lipid oxidation in epididymal white adipose tissue (eWAT) , but significantly increased carnitine palmitoyltransferase-1b (CPT1b) and PPAR gamma coactivator-1 alpha (PGC1 alpha) expression. Notably, CLA increased both mRNA and protein expression of uncoupling protein-1 (UCP1). beta 3-adrenoceptor mRNA and phosphorylated-p38 mitogen activated protein kinase (MAPK) protein levels were not affected by CLA, but were upregulated by LEPTIN. These data suggest the increased CPT1b, PGC1 alpha, and UCP1, in WAT of CLA-fed mice may contribute to the depletion of adipose, and CLA does not appear to increase UCP1 through beta 3-adrenergic signaling. Future studies will focus on understanding how CLA increases mitochondrial oxidation and energy dissipation in white adipose tissue.