Phosphodiesterase 8A Modulates Lipolysis in Primary Brown Adipocytes

Abstract

Brown adipose tissue (BAT) is the primary center of metabolic heat production in mammals during cold‐induced, adaptive thermogenesis. While white fat is an energy "storing" tissue, BAT is known as an energy "wasting" tissue, where the energy from triglyceride breakdown is lost as heat. Intracellular increases in cAMP are known to regulate a number of key processes in BAT, such as acute lipolysis, precursor proliferation and differentiation, and the induction of thermogenic genes including Ucp1. Phosphodiesterases (PDE) are enzymes that catalyze the breakdown of cyclic nucleotides, thereby modulating the second messenger's downstream effects. Here, we present evidence that Phosphodiesterase 8A (PDE8A) is expressed highly in the interscapular BAT of mice, though not expressed in white fat. Utilizing a PDE8A‐/‐ mouse, which has a LacZ‐Neo cassette inserted into the endogenous PDE8A locus, we observe strong β‐Gal activity in BAT. We confirmed PDE8A expression in wild‐type BAT using mRNA, protein, and activity analyses. Preliminary evidence shows that PDE8A ablation modulates lipolysis in response to isoproterenol in isolated adipocytes, suggesting that PDE8A plays a role in the lypolitic component of the thermogenic response in brown fat. Supported by NIH grants DK21723 and GM08392.