title: Dose-dependent effects of neuropeptide Y on the regulation of preadipocyte proliferation and adipocyte lipid synthesis via the PPARγ pathways.
abstract: The objective of this study was to investigate the impact of neuropeptide Y (NPY) on preadipocyte proliferation and differentiation. Preadipocytes were incubated with a range of concentrations of NPY (10(-15)M - 10(-7)M). After NPY-induced differentiation, the extent of preadipocyte adipogenesis was evaluated. The expressions levels of related adipocyte markers such as PPARγ, C/EBPα and DLK-1 were examined by real-time PCR (RT-PCR) or western blot analysis. Furthermore, the mitogen-activated protein kinase (MAPK) signaling pathway proteins were also analyzed by western blot. Our results showed that low doses of NPY stimulated preadipocyte viability and proliferation, while high NPY doses inhibited cell viability. At high concentrations of NPY significantly promoted lipid accumulation and increased the size of lipid droplets. DLK-1 mRNA expression was inhibited, but the expression levels of PPARγ and C/EBPα were increased during differentiation with the presence of high concentration of NPY. High-dose NPY also suppressed the phosphorylation of the extracellular signal-regulated kinase (ERK) 1/2 protein. We conclude that NPY has a biphasic effect on preadipocyte proliferation. A high dose inhibits the proliferation of 3T3-L1 cell while promotes adipocyte differentiation, increasing lipid accumulation especially enlarged lipid droplets' size. NPY may lead to a better understanding for drug development to prevent hyperplastic obesity and hypertrophic obesity.
authors.affiliation: Institute of Metabolism and Endocrinology, the Second Xiang-Ya Hospital of Central South University, Changsha 410011, China.
authors.forename: Hao-Neng
authors.initials: HN
authors.lastname: Tang
authors.forename: Xiao-Fei
authors.initials: XF
authors.lastname: Man
authors.forename: Ya-Qing
authors.initials: YQ
authors.lastname: Liu
authors.forename: Yue
authors.initials: Y
authors.lastname: Guo
authors.forename: Ai-Guo
authors.initials: AG
authors.lastname: Tang
authors.forename: Er-Yuan
authors.initials: EY
authors.lastname: Liao
authors.forename: Hou-De
authors.initials: HD
authors.lastname: Zhou
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D022762:CCAAT-Enhancer-Binding Proteins / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D050356:Lipid Metabolism / Q000187:drug effects; D008055:Lipids / Q000096:biosynthesis*; D051379:Mice; D009478:Neuropeptide Y / Q000008:administration & dosage*; D047495:PPAR gamma / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D022762:CCAAT-Enhancer-Binding Proteins; D008055:Lipids; D009478:Neuropeptide Y; D047495:PPAR gamma