Antilipolytic and adipogenic effects of NPY on white adipose tissue. In the peripheral system, NPY binds to receptors 1, 2 and 5 and affects β-adrenergic receptor (β1-AR, β2-AR and β3-AR; mainly through β2-AR) configuration, the modification thereby leading to improved affinity for Gαi proteins. Subsequently, this activation of inhibitory GTP-binding protein alpha subunit (Gαi) inhibits adenylyl cyclase (AC) and cyclic AMP (cAMP) production. Decreased cellular cAMP levels inhibit protein kinase A (PKA), which phosphorylates and activates hormone-sensitive lipase (HSL). Decreased PKA activity also inhibits phosphorylation of lipid droplet-associated protein perilipin (peri) into PeriA, which controls the magnitude of lipolysis. Lipolysis is catalyzed by 3 lipases. Triacylglycerol is firstly hydrolyzed by adipocyte triglyceride lipase (ATGL) resulting in the formation of diacylglycerol (DAG) and release of a fatty acid (FA). Monoacylglycerol lipase (MGL) catalyzes hydrolysis of MAG, yielding glycerol and a FA. Increased hypothalamic (abbreviated as hypo in the figure) NPY inhibits sympathetic nerve system (SNS) outflow and suppresses catecholamine release, mainly norepinephrine (NE), and thereby their binding to β-adrenergic receptors, which in turn reduces the cAMP-PKA pathway-associated lipolysis. On the other hand, NPY itself in the peripheral system can stimulate ERK-mediated adipogenesis. Through the hypothalamus-SNS-adipose tissue axis, reduced NE enhances adipogenesis via undefined mechanisms. Reduced SNS outflow is compensated for by adrenal medullary catecholamines, primarily epinephrine (EPI), which was also known to stimulate adipogenesis, possibly through NPY regulation. Parts of the figure are adapted from references [71, 72]. “→”: stimulatory effect; “⊣”: inhibitory effect ;“······›”mechanisms unknown; “─··─·›” compensatory effect of EPI secretion.