title: [PPARβ/δ Activation prevents hypertriglyceridemia caused by a high fat diet. Involvement of AMPK and PGC-1α-Lipin1-PPARα pathway].
abstract: BACKGROUND
  Excessive consume of hypercaloric and high in saturated fat food causes an atherogenic dyslipidemia. In this study we analyzed the effects of PPARβ/δ activator GW501516 on the hypertriglyceridemia induced by a high-fat diet.
  
  
  METHODS
  Male mice were randomized in three groups: control (standard chow), high fat diet (HFD, 35% fat by weight, 58% Kcal from fat) and high fat diet plus GW501516 (3mg/Kg/day). Treatment duration was three weeks.
  
  
  RESULTS
  HFD-induced hypertriglyceridemia was accompanied by a reduction in hepatic levels of phospho-AMPK and in PGC-1α and Lipin1 mRNA levels. All these effects were reversed by GW501516 treatment. The lack of changes in phospho-AMPK levels after GW501516 treatment in HFD-fed animals could be the result of an increase in the AMP/ATP ratio. GW501516 treatment also increased Lipin1 protein levels in the nucleus, led to the amplification of the PGC-1α-PPARα pathway and increased PPARα DNA-binding activity, as well as the expression of PPARα-target genes involved in fatty acid oxidation. GW501516 also increased β-hydroxibutirate plasmatic levels, a hepatic β-oxidation end product. Finally, GW501516 increased the hepatic levels of the PPARα endogenous ligand 16:0/18:1-PC and the expression of the VLDL receptor.
  
  
  CONCLUSIONS
  These data indicate that the hypotriglyceridemic effect of GW501516 in mice subjected to HFD-fed mice is accompanied by an increase in phospho-AMPK levels and the amplification of the PGC-1α-Lipin1-PPARα pathway.
authors.affiliation: Unidad de Farmacología, Departamento de Farmacología y Química Terapéutica e Institut de Biomedicina de la UB IBUB, Facultad de Farmacia, Universidad de Barcelona, Barcelona, España.
authors.forename: Emma
authors.initials: E
authors.lastname: Barroso
authors.forename: Alma M
authors.initials: AM
authors.lastname: Astudillo
authors.forename: Jesús
authors.initials: J
authors.lastname: Balsinde
authors.forename: Manuel
authors.initials: M
authors.lastname: Vázquez-Carrera
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000249:Adenosine Monophosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D059305:Diet, High-Fat / Q000009:adverse effects; D004195:Disease Models, Animal; D015228:Hypertriglyceridemia / Q000209:etiology / Q000517:prevention & control*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D009687:Nuclear Proteins / Q000378:metabolism; D047493:PPAR alpha / Q000187:drug effects* / Q000378:metabolism; D047495:PPAR gamma / Q000187:drug effects* / Q000378:metabolism; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D010711:Phosphatidate Phosphatase / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D013844:Thiazoles / Q000494:pharmacology*; D014157:Transcription Factors / Q000378:metabolism
chemical_list: C425931:GW 501516; D009687:Nuclear Proteins; D047493:PPAR alpha; D047495:PPAR gamma; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C485290:Ppargc1a protein, mouse; D012333:RNA, Messenger; D013844:Thiazoles; D014157:Transcription Factors; D000249:Adenosine Monophosphate; D000255:Adenosine Triphosphate; D055372:AMP-Activated Protein Kinases; C418978:Lpin1 protein, mouse; D010711:Phosphatidate Phosphatase
keywords: AMP-activated protein kinase; Cinasa activada por adenosinmonofosfato; Dieta rica en grasa; Dislipidemia; Dyslipidemia; High fat diet; Peroxisome proliferator-activator receptor beta/delta; Receptor activado por proliferadores peroxisómicos β/δ