title: Role of AMPK and PPARγ1 in exercise-induced lipoprotein lipase in skeletal muscle.
abstract: Exercise can effectively ameliorate type 2 diabetes and insulin resistance. Here we show that the mRNA levels of one of peroxisome proliferator-activated receptor (PPAR) family members, PPARγ1, and genes related to energy metabolism, including PPARγ coactivator-1 protein-1α (PGC-1α) and lipoprotein lipase (LPL), increased in the gastrocnemius muscle of habitual exercise-trained mice. When mice were intraperitoneally administered an AMP-activated protein kinase (AMPK) activator 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR), the mRNA levels of the aforementioned three genes increased in gastrocnemius muscle. AICAR treatment to C2C12 differentiated myotubes also increased PPARγ1 mRNA levels, but not PPARα and -δ mRNA levels, concomitant with increased PGC-1α mRNA levels. An AMPK inhibitor, compound C, blocked these AICAR effects. AICAR treatment increased the half-life of PPARγ1 mRNA nearly threefold (4-12 h) by activating AMPK. When C2C12 myoblast cells infected with a PPARγ1 expression lentivirus were differentiated into myotubes, PPARγ1 overexpression dramatically increased LPL mRNA levels more than 40-fold. In contrast, when PPARγ1 expression was suppressed in C2C12 myotubes, LPL mRNA levels were significantly reduced, and the effect of AICAR on increased LPL gene expression was almost completely blocked. These results indicated that PPARγ1 was intimately involved in LPL gene expression in skeletal muscle and the AMPK-PPARγ1 pathway may play a role in exercise-induced LPL expression. Thus, we identified a novel critical role for PPARγ1 in response to AMPK activation for controlling the expression of a subset of genes associated with metabolic regulation in skeletal muscle.
authors.affiliation: Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, Japan; and.
authors.forename: Takashi
authors.initials: T
authors.lastname: Sasaki
authors.forename: Rieko
authors.initials: R
authors.lastname: Nakata
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Inoue
authors.forename: Makoto
authors.initials: M
authors.lastname: Shimizu
authors.forename: Jun
authors.initials: J
authors.lastname: Inoue
authors.forename: Ryuichiro
authors.initials: R
authors.lastname: Sato
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000502:physiology*; D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D004734:Energy Metabolism / Q000187:drug effects / Q000235:genetics; D057809:HEK293 Cells; D006801:Humans; D008071:Lipoprotein Lipase / Q000235:genetics* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism*; D047495:PPAR gamma / Q000502:physiology*; D010805:Physical Conditioning, Animal / Q000502:physiology*; D012265:Ribonucleotides / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
chemical_list: D047495:PPAR gamma; D012265:Ribonucleotides; D000620:Aminoimidazole Carboxamide; D055372:AMP-Activated Protein Kinases; D008071:Lipoprotein Lipase; C031143:AICA ribonucleotide
keywords: AMP-activated protein kinase; C2C12 cells; exercise; lipoprotein lipase; peroxisome proliferator-activated receptor-γ1