title: Hypothalamic AMPK-induced autophagy increases food intake by regulating NPY and POMC expression.
abstract: Hypothalamic AMP-activated protein kinase (AMPK) plays important roles in the regulation of food intake by altering the expression of orexigenic or anorexigenic neuropeptides. However, little is known about the mechanisms of this regulation. Here, we report that hypothalamic AMPK modulates the expression of NPY (neuropeptide Y), an orexigenic neuropeptide, and POMC (pro-opiomelanocortin-α), an anorexigenic neuropeptide, by regulating autophagic activity in vitro and in vivo. In hypothalamic cell lines subjected to low glucose availability such as 2-deoxy-d-glucose (2DG)-induced glucoprivation or glucose deprivation, autophagy was induced via the activation of AMPK, which regulates ULK1 and MTOR complex 1 followed by increased Npy and decreased Pomc expression. Pharmacological or genetic inhibition of autophagy diminished the effect of AMPK on neuropeptide expression in hypothalamic cell lines. Moreover, AMPK knockdown in the arcuate nucleus of the hypothalamus decreased autophagic activity and changed Npy and Pomc expression, leading to a reduction in food intake and body weight. AMPK knockdown abolished the orexigenic effects of intraperitoneal 2DG injection by decreasing autophagy and changing Npy and Pomc expression in mice fed a high-fat diet. We suggest that the induction of autophagy is a possible mechanism of AMPK-mediated regulation of neuropeptide expression and control of feeding in response to low glucose availability.
authors.affiliation: a Department of Brain & Cognitive Sciences , Daegu Gyeongbuk Institute of Science & Technology , Dalseong-gun , Daegu , Korea.
authors.forename: Tae Seok
authors.initials: TS
authors.lastname: Oh
authors.affiliation: a Department of Brain & Cognitive Sciences , Daegu Gyeongbuk Institute of Science & Technology , Dalseong-gun , Daegu , Korea.
authors.forename: Hanchae
authors.initials: H
authors.lastname: Cho
authors.affiliation: a Department of Brain & Cognitive Sciences , Daegu Gyeongbuk Institute of Science & Technology , Dalseong-gun , Daegu , Korea.
authors.forename: Jae Hyun
authors.initials: JH
authors.lastname: Cho
authors.affiliation: a Department of Brain & Cognitive Sciences , Daegu Gyeongbuk Institute of Science & Technology , Dalseong-gun , Daegu , Korea.
authors.forename: Seong-Woon
authors.initials: SW
authors.lastname: Yu
authors.affiliation: a Department of Brain & Cognitive Sciences , Daegu Gyeongbuk Institute of Science & Technology , Dalseong-gun , Daegu , Korea.|b Neurometabolomics Research Center , Daegu Gyeongbuk Institute of Science & Technology , Dalseong-gun , Daegu , Korea.
authors.forename: Eun-Kyoung
authors.initials: EK
authors.lastname: Kim
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000187:drug effects / Q000201:enzymology; D001343:Autophagy / Q000187:drug effects / Q000235:genetics; D000071187:Autophagy-Related Protein 5 / Q000378:metabolism; D000071189:Autophagy-Related Protein-1 Homolog / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D002460:Cell Line; D003847:Deoxyglucose / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects; D004435:Eating / Q000187:drug effects / Q000235:genetics; D004789:Enzyme Activation / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D055785:Gene Knockdown Techniques; D006963:Hyperphagia / Q000473:pathology; D007031:Hypothalamus / Q000201:enzymology*; D008297:Male; D000076222:Mechanistic Target of Rapamycin Complex 1; D008810:Mice, Inbred C57BL; D046912:Multiprotein Complexes / Q000378:metabolism; D009478:Neuropeptide Y / Q000235:genetics* / Q000378:metabolism; D011333:Pro-Opiomelanocortin / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D020123:Sirolimus / Q000494:pharmacology; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
chemical_list: C495773:Atg5 protein, mouse; D000071187:Autophagy-Related Protein 5; D046912:Multiprotein Complexes; D009478:Neuropeptide Y; D012333:RNA, Messenger; D011333:Pro-Opiomelanocortin; D003847:Deoxyglucose; D000071189:Autophagy-Related Protein-1 Homolog; D000076222:Mechanistic Target of Rapamycin Complex 1; D058570:TOR Serine-Threonine Kinases; C112444:Ulk1 protein, mouse; D055372:AMP-Activated Protein Kinases; D020123:Sirolimus
keywords: appetite; autophagy; glucoprivation; glucose deprivation; hypothalamic AMPK; neuropeptide