title: Peripheral administration of TAT-obestatin can influence the expression of liporegulatory genes but fails to affect food intake in mice.
abstract: Obestatin is a 23-amino-acid peptide originally regarded as an anorexigenic factor. However, most of the subsequent studies failed to confirm the initially reported anorexigenic properties of obestatin. Obestatin is incapable of crossing the blood brain barrier (BBB), which may affect its biological function. Here, we report the physiological effects of obestatin in mice after intraperitoneal administration of obestatin conjugated to the cell-permeable peptide TAT, which is capable of delivering different types of proteins through the BBB. Acute peripheral administration of 1 μmol/kg of TAT-obestatin did not influence the 24 h cumulative food intake and body weight gain of mice that were fasted for 18 h. Fed mice were injected intraperitoneally with 100 nmol/kg of TAT-obestatin daily for 25 d. Compared with control groups, on day 3, the gain in body weight was significantly altered; on day 7, abdominal fat mass was remarkably reduced; however, on day 25, there was a surprisingly notable increase in abdominal and epididymal fat mass. In comparison with control groups, on day 25, the expression levels of adiponectin, ADD1, C/EBPα, PPARG and GLUT4 were significantly up-regulated in liver tissues; in white adipose tissue, the expression level of C/EBPα was significantly up-regulated, but adiponectin and GLUT4 were significantly down-regulated. In addition, GPR39, the suspected receptor of obestatin, was up-regulated in white adipose tissue on day 25. These findings suggest that TAT-obestatin might play a role in white adipose tissue metabolism, but its physiological effects on food intake and body weight gain regulation remain unclear.
authors: State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-Sen University, Guangzhou 510006, People's Republic of China.
authors: Guangcai
authors: G
authors: Ren
authors: Zuyong
authors: Z
authors: He
authors: Peiqing
authors: P
authors: Cong
authors: Hu
authors: H
authors: Chen
authors: Yunxue
authors: Y
authors: Guo
authors: Jingwei
authors: J
authors: Yu
authors: Zhiguo
authors: Z
authors: Liu
authors: Qianqian
authors: Q
authors: Ji
authors: Zhenwei
authors: Z
authors: Song
authors: Yaosheng
authors: Y
authors: Chen
mesh_terms: D050153:Abdominal Fat / Q000187:drug effects; D052242:Adiponectin / Q000235:genetics; D052436:Adipose Tissue, White / Q000187:drug effects / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects; D001823:Body Composition / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000235:genetics; D004435:Eating / Q000187:drug effects*; D004822:Epididymis / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects*; D054439:Ghrelin / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D051275:Glucose Transporter Type 4 / Q000235:genetics; D007274:Injections, Intraperitoneal; D008055:Lipids / Q000097:blood / Q000235:genetics; D050155:Lipogenesis / Q000187:drug effects / Q000235:genetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D047495:PPAR gamma / Q000235:genetics; D010446:Peptide Fragments / Q000008:administration & dosage* / Q000737:chemistry; D043562:Receptors, G-Protein-Coupled / Q000235:genetics; D015430:Weight Gain / Q000187:drug effects; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000008:administration & dosage* / Q000737:chemistry; D000099291:Adducins
chemical_list: D052242:Adiponectin; D003598:Cytoskeletal Proteins; D054439:Ghrelin; D051275:Glucose Transporter Type 4; D008055:Lipids; D047495:PPAR gamma; D010446:Peptide Fragments; D043562:Receptors, G-Protein-Coupled; D054322:tat Gene Products, Human Immunodeficiency Virus; C581701:Add1 protein, mouse; D000099291:Adducins; C499919:Adipoq protein, mouse; C512928:GPR39 protein, mouse; C495693:Slc2a4 protein, mouse; C490722:tat peptide (49-57), Human immunodeficiency virus 1