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Publication : Skeletal muscle AMP-activated protein kinase γ1(H151R) overexpression enhances whole body energy homeostasis and insulin sensitivity.

First Author  Schönke M Year  2015
Journal  Am J Physiol Endocrinol Metab Volume  309
Issue  7 Pages  E679-90
PubMed ID  26306597 Mgi Jnum  J:228351
Mgi Id  MGI:5706851 Doi  10.1152/ajpendo.00195.2015
Citation  Schonke M, et al. (2015) Skeletal muscle AMP-activated protein kinase gamma1(H151R) overexpression enhances whole body energy homeostasis and insulin sensitivity. Am J Physiol Endocrinol Metab 309(7):E679-90
abstractText  AMP-activated protein kinase (AMPK) is a major sensor of energy homeostasis and stimulates ATP-generating processes such as lipid oxidation and glycolysis in peripheral tissues. The heterotrimeric enzyme consists of a catalytic alpha-subunit, a beta-subunit that is important for enzyme activity, and a noncatalytic gamma-subunit that binds AMP and activates the AMPK complex. We generated a skeletal muscle Cre-inducible transgenic mouse model expressing a mutant gamma1-subunit (AMPKgamma1(H151R)), resulting in chronic AMPK activation. The expression of the predominant AMPKgamma3 isoform in skeletal muscle was reduced in extensor digitorum longus (EDL) muscle (81-83%) of AMPKgamma1(H151R) transgenic mice, whereas the abundance and phosphorylation of the AMPK target acetyl-CoA carboxylase was increased in tibialis anterior muscle. Glycogen content was increased 10-fold in gastrocnemius muscle. Whole body carbohydrate oxidation was increased by 11%, and whereas glucose tolerance was unaffected, insulin sensitivity was increased in AMPKgamma1(H151R) transgenic mice. Furthermore, perigonadal white adipose tissue mass and serum leptin were reduced in female AMPKgamma1(H151R) transgenic mice by 38 and 51% respectively. Conversely, in male AMPKgamma1(H151R) transgenic mice, food intake was increased (14%), but body weight and body composition were unaltered, presumably because of increased energy expenditure. In conclusion, transgenic activation of skeletal muscle AMPKgamma1 in this model plays an important sex-specific role in skeletal muscle metabolism and whole body energy homeostasis.
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