title: NPY antagonism reduces adiposity and attenuates age-related imbalance of adipose tissue metabolism.
abstract: An orexigenic hormone, neuropeptide Y (NPY), plays a role not only in the hypothalamic regulation of appetite, but also in the peripheral regulation of lipid metabolism. However, the intracellular mechanisms triggered by NPY to regulate lipid metabolism are poorly understood. Here we report that NPY deficiency reduces white adipose tissue (WAT) mass and ameliorates the age-related imbalance of adipose tissue metabolism in mice. Gene expression involved in adipogenesis/lipogenesis was found to decrease, whereas proteins involved in lipolysis increased in gonadal WAT (gWAT) of NPY-knockout mice. These changes were associated with an activated SIRT1- and PPARγ-mediated pathway. Moreover, the age-related decrease of de novo lipogenesis in gWAT and thermogenesis in inguinal WAT was inhibited by NPY deficiency. Further analysis using 3T3-L1 cells showed that NPY inhibited lipolysis through the Y1 receptor and enhanced lipogenesis following a reduction in cAMP response element-binding protein (CREB) and SIRT1 protein expression. Therefore, NPY appears to act as a key regulator of adipose tissue metabolism via the CREB-SIRT1 signaling pathway. Taken together, NPY deficiency reduces adiposity and ameliorates the age-related imbalance of adipose tissue metabolism, suggesting that antagonism of NPY may be a promising target for drug development to prevent age-related metabolic diseases.
authors.affiliation: Department of Pathology, Graduate School of Biomedical Sciences, Nagasaki University School of Medicine, Nagasaki City, Japan psj10262000@yahoo.co.kr.
authors.forename: Seongjoon
authors.initials: S
authors.lastname: Park
authors.affiliation: Department of Pathology, Graduate School of Biomedical Sciences, Nagasaki University School of Medicine, Nagasaki City, Japan.
authors.forename: Chika
authors.initials: C
authors.lastname: Fujishita
authors.affiliation: Department of Pathology, Graduate School of Biomedical Sciences, Nagasaki University School of Medicine, Nagasaki City, Japan.
authors.forename: Toshimitsu
authors.initials: T
authors.lastname: Komatsu
authors.affiliation: Department of Pathology, Graduate School of Biomedical Sciences, Nagasaki University School of Medicine, Nagasaki City, Japan.
authors.forename: Sang Eun
authors.initials: SE
authors.lastname: Kim
authors.affiliation: Department of Pathology, Graduate School of Biomedical Sciences, Nagasaki University School of Medicine, Nagasaki City, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Chiba
authors.affiliation: Department of Pathology, Graduate School of Biomedical Sciences, Nagasaki University School of Medicine, Nagasaki City, Japan.
authors.forename: Ryoichi
authors.initials: R
authors.lastname: Mori
authors.affiliation: Department of Pathology, Graduate School of Biomedical Sciences, Nagasaki University School of Medicine, Nagasaki City, Japan.
authors.forename: Isao
authors.initials: I
authors.lastname: Shimokawa
mesh_terms: D041721:3T3-L1 Cells / Q000378:metabolism; D000273:Adipose Tissue / Q000378:metabolism*; D050154:Adiposity / Q000502:physiology*; D000367:Age Factors; D000818:Animals; D001483:Base Sequence; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D017931:DNA Primers; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009478:Neuropeptide Y / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000502:physiology; D016133:Polymerase Chain Reaction
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D017931:DNA Primers; D009478:Neuropeptide Y
keywords: adipocytes; lipid metabolism; sirtuins