Growth Hormone Increases mRNA Levels of PPARδ and Foxo1 in Skeletal Muscle of Growth Hormone Deficient lit/lit Mice

• Published in: Endocrine Journal Vol. 56; no. 1; pp. 141 - 147
• Main Authors: KIM, Dong-Sun, ITOH, Emina, IIDA, Keiji, THORNER, Michael O
• Format: Journal Article
• Language: English
• Published: The Japan Endocrine Society 20.02.2009
• Subjects: Foxo1; Growth hormone; PPAR-delta; Skeletal muscle
• ISSN: 0918-8959; 1348-4540
• DOI: 10.1507/endocrj.K08E-219

GH plays an important role in lipid metabolism as a partitioning hormone. PPARδ 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 PPARδ 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. PPARδ 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 PPARδ 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 PPARδ 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.