title: Neuropeptide Y resists excess loss of fat by lipolysis in calorie-restricted mice: a trait potential for the life-extending effect of calorie restriction.
abstract: Neuropeptide Y (NPY) is an orexigenic peptide that plays an essential role in caloric restriction (CR)-mediated lifespan extension. However, the mechanisms underlying the NPY-mediated effects in CR are poorly defined. Here, we report that NPY deficiency in male mice during CR increases mortality in association with lipodystrophy. NPY-/-mice displayed a rapid decrease in body weight and fat mass, as well as increased lipolysis during CR. These alterations in fat regulation were inhibited by the lipolysis inhibitor, acipimox, a treatment associated with reduced mortality. The lipolytic/thermogenic signaling, β3-adrenergic receptor/hormone sensitive lipase, was markedly activated in white adipose tissue of NPY-/-mice compared with that of NPY+/+mice, and thermogenesis was controlled by NPY under negative energy balance. These results demonstrate the critical role of NPY in the regulation of lipid metabolic homeostasis and survival via control of lipolysis and thermogenesis in a state of negative energy balance.
authors.affiliation: Department of Pathology, Nagasaki University School of Medicine, Graduate School of Biomedical Sciences, 1-12-4 Sakamoto, Nagasaki, 852-8523, Japan.
authors.forename: Seongjoon
authors.initials: S
authors.lastname: Park
authors.affiliation: Department of Pathology, Nagasaki University School of Medicine, Graduate School of Biomedical Sciences, 1-12-4 Sakamoto, Nagasaki, 852-8523, Japan.
authors.forename: Toshimitsu
authors.initials: T
authors.lastname: Komatsu
authors.affiliation: Department of Pathology, Nagasaki University School of Medicine, Graduate School of Biomedical Sciences, 1-12-4 Sakamoto, Nagasaki, 852-8523, Japan.
authors.forename: Sang Eun
authors.initials: SE
authors.lastname: Kim
authors.affiliation: Department of Pathology, Nagasaki University School of Medicine, Graduate School of Biomedical Sciences, 1-12-4 Sakamoto, Nagasaki, 852-8523, Japan.|Department of Plastic and Reconstructive Surgery, Nagasaki University School of Medicine, Graduate School of Biomedical Sciences, 1-12-4 Sakamoto, Nagasaki, 852-8523, Japan.
authors.forename: Katsuya
authors.initials: K
authors.lastname: Tanaka
authors.affiliation: Department of Pathology, Nagasaki University School of Medicine, Graduate School of Biomedical Sciences, 1-12-4 Sakamoto, Nagasaki, 852-8523, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Hayashi
authors.affiliation: Department of Pathology, Nagasaki University School of Medicine, Graduate School of Biomedical Sciences, 1-12-4 Sakamoto, Nagasaki, 852-8523, Japan.
authors.forename: Ryoichi
authors.initials: R
authors.lastname: Mori
authors.affiliation: Department of Pathology, Nagasaki University School of Medicine, Graduate School of Biomedical Sciences, 1-12-4 Sakamoto, Nagasaki, 852-8523, Japan.
authors.forename: Isao
authors.initials: I
authors.lastname: Shimokawa
mesh_terms: D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D050156:Adipogenesis / Q000187:drug effects; D052436:Adipose Tissue, White / Q000187:drug effects / Q000378:metabolism; D050154:Adiposity / Q000187:drug effects; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D031204:Caloric Restriction; D048429:Cell Size / Q000187:drug effects; D004734:Energy Metabolism / Q000187:drug effects; D008017:Life Expectancy; D008066:Lipolysis / Q000187:drug effects; D008297:Male; D051379:Mice; D008954:Models, Biological; D009026:Mortality; D009478:Neuropeptide Y / Q000172:deficiency / Q000378:metabolism*; D011719:Pyrazines / Q000494:pharmacology; D022702:Receptors, Adrenergic, beta-3 / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D002787:Sterol Esterase / Q000378:metabolism; D022722:Thermogenesis / Q000187:drug effects
chemical_list: D009478:Neuropeptide Y; D011719:Pyrazines; D022702:Receptors, Adrenergic, beta-3; D002787:Sterol Esterase; C027696:acipimox
keywords: adipose tissue; aging; calorie restriction; lipolysis; neuropeptide Y