A Novel Regulatory Function for p130 in Adipocyte Fatty Acid Metabolism

Understanding the complex control mechanisms governing fatty acid synthesis and mobilization holds prognostic and therapeutic potential in treating metabolic diseases such as obesity and diabetes. Our data has uncovered a novel function for the transcriptional co-repressor p130 in adipocytes. In particular, we found that the subcellular localization of p130 supports fatty acid metabolism. Indeed, stimulating lipogenesis increased p130 levels in the mitochondria. Here it interacted at the D-loop regulatory region of mitochondrial DNA, repressing genes involved in oxidative phosphorylation. This could allow the intermediates of the TCA cycle to be utilized for lipid synthesis in lieu of energy production. Conversely, inducing lipolysis via 3-adrenergic activation in white adipocytes or a physiological challenge imposed by fasting, decreased p130 levels in the mitochondria, concomitant with increased mitochondrial-encoded gene expression. Unexpectedly, 3-adrenergic stimulation showed the reverse effect in brown adipocytes. Our results provide valuable insight for deconstructing the intricate metabolic framework of adipocytes.