Regulation of Adipocyte Lipolysis • Catecholamines – Epinephrine & Norepinephrine • Beta Adrenergic Receptors – Stimulate • Alpha Adrenergic Receptors – Inhibit • Insulin – Inhibitory Catecholamines • Stimulatory – B-Adrenergic Receptors – Activates Stimulatory GProtein – Activates Adenylate Cyclase – Generates cAMP – Activates cAMP-dependent protein kinase – Phosphorylates HSL & Perilipins – Break down triglycerides • Inhibitory – A-Adrenergic Receptors – Activates Inhibitory G-protein – Inhibits Adenylate Cyclase •Catecholamines stimulate HSL to break down triglycerides to fatty acids and glycerol •Fatty acids and glycerol are released into the blood and circulated to other body tissues ATGL • Adipose Triglyceride Lipase – Enzyme that may be responsible for catalyzing the initial steps of triglyceride hydrolysis. – Zimmermann et al. (2004) • HSL knock-out mice showed an accumulation of diglycerides, suggesting that additional lipases may be present that can hydrolyze the first ester bond of triglycerides – Still controversial Insulin Lipoprotein Lipase (LPL) Hydrolyzes Plasma Triglycerides Phosphatidylinositol 3-Kinase (PI3K) Phosphorylates Phosphodiesterase-3 Into Degrades FFA cAMP Insulin & LPL PI3K Insulin Phosphorylates • LPL – Hydrolyzes triglycerides in the blood to increase FFA levels • PI3K – Inhibits lipolysis in adipose cells – Mediates insulinstimulated glucose uptake Phosphodiestesterase-3 Degrades