title: The role of nitric oxide signaling in food intake; insights from the inner mitochondrial membrane peptidase 2 mutant mice.
abstract: Reactive oxygen species have been implicated in feeding control through involvement in brain lipid sensing, and regulating NPY/AgRP and pro-opiomelanocortin (POMC) neurons, although the underlying mechanisms are unclear. Nitric oxide is a signaling molecule in neurons and it stimulates feeding in many species. Whether reactive oxygen species affect feeding through interaction with nitric oxide is unclear. We previously reported that Immp2l mutation in mice causes excessive mitochondrial superoxide generation, which causes infertility and early signs of aging. In our present study, reduced food intake in mutant mice resulted in significantly reduced body weight and fat composition while energy expenditure remained unchanged. Lysate from mutant brain showed a significant decrease in cGMP levels, suggesting insufficient nitric oxide signaling. Thus, our data suggests that reactive oxygen species may regulate food intake through modulating the bioavailability of nitric oxide.
authors.affiliation: Wake Forest University Health Sciences, Institute for Regenerative Medicine, Winston-Salem, NC 27157, United States ; Department of Human Anatomy and Embryology, The Second Military Medical University, Shanghai 200433, China.
authors.forename: Changjie
authors.initials: C
authors.lastname: Han
authors.forename: Qingguo
authors.initials: Q
authors.lastname: Zhao
authors.forename: Baisong
authors.initials: B
authors.lastname: Lu
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000166:cytology / Q000187:drug effects; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000378:metabolism; D004435:Eating / Q000187:drug effects* / Q000235:genetics; D010450:Endopeptidases / Q000235:genetics*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D008297:Male; D051379:Mice; D024101:Mitochondrial Proteins / Q000235:genetics*; D009154:Mutation; D009569:Nitric Oxide / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D024101:Mitochondrial Proteins; D017382:Reactive Oxygen Species; D009569:Nitric Oxide; D010450:Endopeptidases; C568497:inner mitochondrial membrane peptidase 2-like protein, mouse; D006152:Cyclic GMP
keywords: ADSC, adipose-derived stromal cells; AMPK, AMP-activated protein kinase.; AgRP, agouti related protein; CART, cocaine- and amphetamine-regulated transcript; CYC1, cytochrome c1; Energy expenditure; Food intake; GPD2, mitochondrial glycerol phosphate dehydrogenase; Immp2l; Immp2l, IMP2 inner mitochondrial membrane peptidase-like; Mutant mice; NO, nitric oxide; NOS, nitric oxide synthase; NPY, neuropeptide Y; Nitric oxide; POMC, pro-opiomelanocortin; ROS, reactive oxygen species; Superoxide; UCP2, uncoupling protein 2; cGMP, cyclic guanosine monophosphate