title: Role of hypothalamic proopiomelanocortin neuron autophagy in the control of appetite and leptin response.
abstract: Autophagy is a catabolic cellular process involving the degradation of the cell's own components. Although the role of autophagy of diverse tissues in body metabolism has been investigated, the importance of autophagy in hypothalamic proopiomelanocortin (POMC) neurons, key regulators of energy balance, has not been addressed. The role of autophagy in leptin sensitivity that is critical for the control of body weight and appetite has also not been investigated. We produced mice with specific deletion of autophagy-related 7 (Atg7), an essential autophagy gene, in hypothalamic POMC neurons (Atg7(ΔPOMC) mice). Atg7 expression was deficient in the arcuate nucleus of the hypothalamus of Atg7(ΔPOMC) mice. p62, a specific substrate of autophagy, accumulated in the hypothalamus of Atg7(ΔPOMC) mice, which colocalized with ubiquitin. Atg7(ΔPOMC) mice had increased body weight due to increased food intake and decreased energy expenditure. Atg7(ΔPOMC) mice were not more prone to diet-induced obesity compared with control mice but more susceptible to hyperglycemia after high-fat diet. The ability of leptin to suppress fasting-elicited hyperphagia and weight gain during refeeding was attenuated in Atg7(ΔPOMC) mice. Deficient autophagy did not significantly affect POMC neuron number but impaired leptin-induced signal transducer and activation of transcription 3 activation. Our findings indicate a critical role for autophagy of POMC neurons in the control of energy homeostasis and leptin signaling.
authors.affiliation: Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 135-710, Korea.
authors.forename: Wenying
authors.initials: W
authors.lastname: Quan
authors.forename: Hyun-Kyong
authors.initials: HK
authors.lastname: Kim
authors.forename: Eun-Yi
authors.initials: EY
authors.lastname: Moon
authors.forename: Su Sung
authors.initials: SS
authors.lastname: Kim
authors.forename: Cheol Soo
authors.initials: CS
authors.lastname: Choi
authors.forename: Masaaki
authors.initials: M
authors.lastname: Komatsu
authors.forename: Yeon Taek
authors.initials: YT
authors.lastname: Jeong
authors.forename: Moon-Kyu
authors.initials: MK
authors.lastname: Lee
authors.forename: Kwang-Won
authors.initials: KW
authors.lastname: Kim
authors.forename: Min-Seon
authors.initials: MS
authors.lastname: Kim
authors.forename: Myung-Shik
authors.initials: MS
authors.lastname: Lee
mesh_terms: D000818:Animals; D001069:Appetite Regulation / Q000502:physiology*; D001343:Autophagy / Q000235:genetics / Q000502:physiology*; D000071193:Autophagy-Related Protein 7; D001835:Body Weight / Q000502:physiology; D004195:Disease Models, Animal; D004435:Eating / Q000502:physiology; D004734:Energy Metabolism / Q000502:physiology; D017353:Gene Deletion; D007031:Hypothalamus / Q000473:pathology*; D020738:Leptin / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000502:physiology; D009474:Neurons / Q000378:metabolism* / Q000473:pathology*; D009765:Obesity / Q000503:physiopathology; D011333:Pro-Opiomelanocortin / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology
chemical_list: C502661:Atg7 protein, mouse; D020738:Leptin; D008869:Microtubule-Associated Proteins; D011333:Pro-Opiomelanocortin; D000071193:Autophagy-Related Protein 7