Lipolytic Products Activate Peroxisome Proliferator-activated Receptor (PPAR) α and δ in Brown Adipocytes to Match Fatty Acid Oxidation with Supply
作者： Emilio P. Mottillo , Ainsley E. Bloch , Todd Leff , James G. Granneman
关键词: Adipose triglyceride lipase 、 Thermogenin 、 Brown adipose tissue 、 Biochemistry 、 Peroxisome proliferator-activated receptor 、 Fatty acid 、 Gene knockdown 、 Biology 、 Lipid droplet 、 Beta oxidation
摘要: β-adrenergic receptors (β-ARs) promote brown adipose tissue (BAT) thermogenesis by mobilizing fatty acids and inducing the expression of oxidative genes. β-AR activation increases genes elevating cAMP, but whether lipolytic products can modulate gene is not known. This study examined role that triglyceride lipase (ATGL) hormone-sensitive (HSL) plays in induction expression. Activation adipocytes agonism or 8-bromo-cyclic AMP increased PGC1α, PDK4, PPARα, uncoupling protein 1 (UCP1), neuron-derived orphan receptor-1 (NOR-1), concurrent inhibition HSL reduced UCP1 NOR-1. Similar results were observed BAT mice following pharmacological genetic with stable knockdown ATGL. Conversely, treatments increase endogenous elevated Pharmacological antagonism siRNA indicate PPARα PPARδ agonism. Using a live cell fluorescent reporter assay PPAR activation, we demonstrated ligands for -δ, PPARγ, rapidly generated at lipid droplet surface could transcriptionally activate -δ. Knockdown ATGL cAMP-mediated involved acid oxidation phosphorylation. Consequently, maximal acids, pyruvate, response to cAMP stimulation. Overall, adipocytes, thereby expanding capacity match enhanced supply.
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