title: Piperine reverses high fat diet-induced hepatic steatosis and insulin resistance in mice.
abstract: This study examined the effect of piperine on hepatic steatosis and insulin resistance induced in mice by feeding a high-fat diet (HFD) for 13 weeks and elucidated potential underlying molecular mechanisms. Administration of piperine (50 mg/kg body weight) to mice with HFD-induced hepatic steatosis resulted in a significant increase in plasma adiponectin levels. Also, elevated plasma concentrations of insulin and glucose and hepatic lipid levels induced by feeding a HFD were reversed in mice when they were administered piperine. However, piperine did not reduce body weight and other biochemical markers to an extent where they became equal to the levels found in the CD-fed mice. Piperine reversed HFD-induced down-regulation of adiponecitn-AMP-activated protein kinase (AMPK) signalling molecules which play an important role in mediating lipogenesis, fatty acid oxidation and insulin signalling in the livers of mice. The expressions of lipogenic target genes were decreased, whereas the expression of carnitine palmitoyltransferase 1 (CPT1) gene involved in fatty acid oxidation was increased in the livers of the Pin50 group. Piperine significantly decreased the phosphorylation of insulin receptor substrate-1 (IRS-1) compared with the HFD-fed mice. Administration of piperine appeared to reverse preexisting HFD-induced hepatic steatosis and insulin resistance, probably by activation of adiponectin-AMPK signalling in mice.
authors.affiliation: Department of Food and Nutrition, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-749, Republic of Korea.
authors.forename: Seoyoon
authors.initials: S
authors.lastname: Choi
authors.forename: Youngshim
authors.initials: Y
authors.lastname: Choi
authors.forename: Yeji
authors.initials: Y
authors.lastname: Choi
authors.forename: Sohee
authors.initials: S
authors.lastname: Kim
authors.forename: Jeehee
authors.initials: J
authors.lastname: Jang
authors.forename: Taesun
authors.initials: T
authors.lastname: Park
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D052242:Adiponectin / Q000378:metabolism; D000470:Alkaloids / Q000008:administration & dosage*; D000818:Animals; D052117:Benzodioxoles / Q000008:administration & dosage*; D059305:Diet, High-Fat / Q000009:adverse effects; D005234:Fatty Liver / Q000188:drug therapy* / Q000378:metabolism*; D006801:Humans; D007333:Insulin Resistance; D050155:Lipogenesis / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D029222:Piper nigrum / Q000737:chemistry*; D010880:Piperidines / Q000008:administration & dosage*; D010936:Plant Extracts / Q000008:administration & dosage*; D053284:Polyunsaturated Alkamides / Q000008:administration & dosage*; D014280:Triglycerides / Q000378:metabolism
chemical_list: D052242:Adiponectin; D000470:Alkaloids; D052117:Benzodioxoles; D010880:Piperidines; D010936:Plant Extracts; D053284:Polyunsaturated Alkamides; D014280:Triglycerides; D055372:AMP-Activated Protein Kinases; C008922:piperine
keywords: AKT; ALT; AMP-activated protein kinase; AMPK; AST; AUC; AdipoR1; AdipoR2; Adiponectin-AMPK signalling; CD36; CD36 antigen; CPT1; FFA; Fatty acid oxidation; Fatty liver; G6Pase; GAPDH; GLUT2; HFD; IRS1; Insulin signalling; LXRα; Lipogenesis; PEPCK; RT-PCR; S6 kinase 1; S6K1; SREBP1c; aP2; adipocyte protein 2; adiponectin receptor-1; adiponectin receptor-2; alanine aminotransferase; area under the curve; aspartate aminostransferase; carnitine palmitoyltransferase 1; free fatty acid; glucose transporter-2; glucose-6-phosphate dehydrogenase; glyceraldehyde-3-phosphate dehydrogenase; high-fat diet; insulin receptor substrate-1; leptin; lipoprotein lipase; liver X receptor alpha; phosphoenolpyruvate carboxykinase; protein kinase B; reverse transcription-polymerase chain reaction; sterol regulatory element binding protein-1c