Hypothalamic AMPK as a Regulator of Energy Homeostasis

Figure 3

The physiological effects of hypothalamic AMPK. Activated in energy depletion conditions, hypothalamic AMP-activated protein kinase (AMPK) restores energy homeostasis by promoting appetite and reducing energy output. Activated hypothalamic AMPK stimulates the orexigenic neuropeptides leading to enhanced food intake and inhibits anorexigenic neuropeptide suppressing food intake. The mammalian target of rapamycin (mTOR), suppressed by the activation of AMPK, also decreases feeding behavior under the effect of leptin. AMPK activity can induce appetite via the inhibition of malonyl-CoA and activation of carnitine palmitoyltransferase- (CPT-) 1. The inhibition of AMPK on malonyl-CoA can lead to decreased fatty acid synthesis and increased β-oxidation. Furthermore, increased β-oxidation could result in the induction of orexigenic gene expression. Besides that, AMPK activation through the sympathetic nerve can reduce thermogenesis and decrease energy expenditure. Additionally, activated hypothalamic AMPK can lead to enhanced glucose production. AgRP, agouti-related protein; NPY, neuropeptide Y; POMC, proopiomelanocortin; TSC2, tuberous sclerosis complex 2; hVps34, mammalian vacuolar protein sorting 34 homologue; ACC, acetyl-CoA carboxylase; FAS, fatty acid synthase; Rpa, raphe pallidus; IO, inferior olive; β3AR, β3-adrenergic receptor; UCP1, uncoupling protein 1; PGC1α, peroxisome proliferator-activated receptor-gamma coactivator 1 alpha.