Growth hormone increases mRNA levels of PPARδ and foxo 1 in skeletal muscle of growth hormone deficient lit/lit mice

Abstract

GH plays an important role in lipid metabolism as a partitioning hormone. PPARS 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 PPARS 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 litl+ 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. PPARS mRNA was increased in vehicle-treated lit/lit mice compared to vehicle-treated litl+ mice (1.67 fold, P<0.05). lit/ lit mice treated with GH showed a further increase in PPARS mRNA levels (2.83 fold vs. vehicle-treated litl+ mice, P<0.001). mRNA levels of Foxo 1 were increased in vehicle-treated lit/lit mice compared to vehicle-treated litl+ mice (1.74 fold, P<0.05). lit/lit mice treated with GH showed a further increase in Foxo l mRNA levels (6.30 fold vs. vehicle- treated litl+ 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 litl+ mice. This reached statistical significance in GH-treated lit/lit mice compared to vehicle- treated litl+ mice (2.11 fold, P<0.05). In summary, mRNA levels of PPARS and Foxo 1 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.