title: BAIBA attenuates insulin resistance and inflammation induced by palmitate or a high fat diet via an AMPK-PPARδ-dependent pathway in mice.
abstract: OBJECTIVE
  We explored the effects of β-aminoisobutyric acid (BAIBA) on hyperlipidaemic-condition-induced insulin resistance and inflammation as mediated through a signalling pathway involving AMP-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor δ (PPARδ).
  
  
  METHODS
  Mouse skeletal muscle C2C12 cells and C57BL/6J mice were treated with palmitate or a high-fat diet (HFD) and BAIBA. Inflammation and the expression of genes associated with insulin signalling were determined by western blot and quantitative real-time PCR. Selected genes from candidate pathways were evaluated by small interfering (si)RNA knockdown and specific inhibitors.
  
  
  RESULTS
  BAIBA treatment ameliorated impairment of insulin receptor substrate (IRS)-1/Akt-mediated insulin signalling in palmitate-treated C2C12 myocytes and in skeletal muscle of HFD-fed mice. In addition, BAIBA treatment reversed HFD-induced increases in body weight and improved impaired glucose tolerance in mice. In vitro and in vivo, inhibitory κBα (IκBα) phosphorylation, nuclear factor κB (NFκB) nuclear translocation and downstream inflammatory cytokines were significantly suppressed by BAIBA. Furthermore, BAIBA treatment significantly induced AMPK phosphorylation and expression of PPARδ in C2C12 myocytes and in skeletal muscle of mice. Both compound C, an AMPK inhibitor, and Pparδ (also known as Ppard) siRNA abrogated the inhibitory effects of BAIBA on palmitate-induced inflammation and insulin resistance. BAIBA significantly induced the expression of genes associated with fatty acid oxidation, such as carnitine palmitoyltransferase 1 (Cpt1), acyl-CoA oxidase (Aco; also known as Acox1) and fatty acid binding protein 3 (Fabp3); this effect of BAIBA was significantly reduced by compound C and Pparδ siRNA.
  
  
  CONCLUSIONS
  These results are the first to demonstrate that BAIBA attenuates insulin resistance, suppresses inflammation and induces fatty acid oxidation via the AMPK-PPARδ pathway in skeletal muscle.
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, Korea University Guro Hospital, 80 Guro-Dong, Guro-Gu, Seoul, 152-050, Republic of Korea.
authors.forename: Tae Woo
authors.initials: TW
authors.lastname: Jung
authors.forename: Hwan-Jin
authors.initials: HJ
authors.lastname: Hwang
authors.forename: Ho Cheol
authors.initials: HC
authors.lastname: Hong
authors.forename: Hye Jin
authors.initials: HJ
authors.lastname: Yoo
authors.forename: Sei Hyun
authors.initials: SH
authors.lastname: Baik
authors.forename: Kyung Mook
authors.initials: KM
authors.lastname: Choi
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D021581:Active Transport, Cell Nucleus; D000621:Aminoisobutyric Acids / Q000737:chemistry*; D000818:Animals; D002334:Carnitine O-Palmitoyltransferase / Q000378:metabolism; D003920:Diabetes Mellitus / Q000378:metabolism; D059305:Diet, High-Fat / Q000009:adverse effects*; D005227:Fatty Acids / Q000737:chemistry; D005786:Gene Expression Regulation; D005951:Glucose Tolerance Test; D007249:Inflammation / Q000503:physiopathology*; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018485:Muscle Fibers, Skeletal / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D010100:Oxygen / Q000737:chemistry; D010168:Palmitates / Q000009:adverse effects*; D034741:RNA, Small Interfering / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D000621:Aminoisobutyric Acids; D005227:Fatty Acids; D007328:Insulin; D016328:NF-kappa B; D010168:Palmitates; C091778:Ppard protein, mouse; D034741:RNA, Small Interfering; D018160:Receptors, Cytoplasmic and Nuclear; D002334:Carnitine O-Palmitoyltransferase; D055372:AMP-Activated Protein Kinases; D010100:Oxygen; C033435:3-aminoisobutyric acid