Effect of palmitate on the metabolic fate of leucine and vice versa in primary adipocytes of a rat model of diet‐induced obsesity (575.7)

Abstract

Metabolic profiling studies have spotlighted altered fatty acid (FA) or branched chain amino acid (BCAA) oxidation that marks the obese and insulin‐resistant phenotype. Interestingly, mRNA expression of Carnitine palmitoyltransferase I (CPT1) ‐the rate‐limiting enzyme of FA oxidation‐ and Isovaleryl‐CoA dehydrogenase (IVDH) ‐a mitochondrial enzyme involved in BCAA oxidation‐ are inversely correlated in the livers of 41 recombinant inbred mouse strains of the BxD genetic reference population (http://www.genenetwork.org/). The inverse correlation between CPT1 and IVDH suggest that a high rate of FA oxidation could decrease BCAA oxidation and vice versa. To test this hypothesis, we have evaluated the effect of increasing concentrations of palmitate or leucine in the metabolic fate of leucine or palmitate in primary adipocytes of a rat model of diet‐induced obsesity. We incubated primary adipocytes with: 1) 0, 250, 500 or 1000 µM of palmitate and evaluated the oxidation, incorporation to lipids or proteins of [U‐14C]‐leucine; or 2) 0, 250, 500 and 1000 µM of leucine and determined the oxidation, incorporation to lipids or proteins of [1‐14C]‐palmitic acid. Interstingly, palmitate increased leucine oxidation and decreased its incorporation to lipids and proteins in a dose‐dependent manner. Furthermore, leucine decreased both palmitate oxidation and its incorporation to lipids and proteins in a dose‐dependent manner. Overall, our results demonstrate that palmitate affects the metabolic fate of leucine and that leucine modifies the metabolic fate of palmitate in primary adipocytes of a rat model of diet‐induced obsesity.Grant Funding Source: CONACYT 155949