Growth hormone increases mRNA levels of PPARdelta and Foxo1 in skeletal muscle of growth hormone deficient lit/lit mice.
GH plays an important role in lipid metabolism as a partitioning hormone. PPARdelta regulates lipid oxidation in skeletal muscle and is activated by several physiological ligands including fatty acids. To investigate whether GH has an effect on the regulation of transcription of PPARdelta and other genes involved in energy metabolism in skeletal muscle, mRNA levels were studied by real-time RT-PCR in lit/lit mice (isolated GH deficiency) and lit/+ mice controls (normal GH levels). Mice received either a single bolus (120 ng/g) of rat GH or vehicle, and skeletal muscle was collected 4h later. PPARdelta mRNA was increased in vehicle-treated lit/lit mice compared to vehicle-treated lit/+ mice (1.67 fold, P<0.05). lit/lit mice treated with GH showed a further increase in PPARdelta mRNA levels (2.83 fold vs. vehicle-treated lit/+ mice, P<0.001). mRNA levels of Foxo1 were increased in vehicle-treated lit/lit mice compared to vehicle-treated lit/+ mice (1.74 fold, P<0.05). lit/lit mice treated with GH showed a further increase in Foxo1 mRNA levels (6.30 fold vs. vehicle-treated lit/+ mice, P<0.001). mRNA levels of acyl CoA-oxidase showed a trend to be higher in vehicle-treated lit/lit mice compared to vehicle-treated lit/+ mice. This reached statistical significance in GH-treated lit/lit mice compared to vehicle-treated lit/+ mice (2.11 fold, P<0.05). In summary, mRNA levels of PPARdelta and Foxo1 were increased in skeletal muscle of GH-deficient mice, and further acutely increased by GH administration. These results suggest that GH plays a relevant role in the lipid catabolism in skeletal muscle.
Kim
Dong-Sun
DS
Division of Endocrinology and Metabolism, University of Virginia, VA 22903, USA.
Itoh
Emina
E
Iida
Keiji
K
Thorner
Michael O
MO
D042962:Acyl-CoA Oxidase / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004393:Dwarfism, Pituitary / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors / Q000235:genetics* / Q000378:metabolism; D013006:Growth Hormone / Q000494:pharmacology*; D006720:Homozygote; D007328:Insulin / Q000097:blood; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism; D047493:PPAR alpha / Q000235:genetics / Q000378:metabolism; D047494:PPAR delta / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; C467200:Foxo1 protein, mouse; D007328:Insulin; D047493:PPAR alpha; D047494:PPAR delta; D012333:RNA, Messenger; D051780:Sterol Regulatory Element Binding Protein 1; D013006:Growth Hormone; D042962:Acyl-CoA Oxidase