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Am J Physiol Endocrinol Metab. 2015 Oct 1;309(7):E679-90. doi: 10.1152/ajpendo.00195.2015. Epub 2015 Aug 25.

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

Author information

1
Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden;
2
Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan; and.
3
Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
4
Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; marie.bjornholm@ki.se.

Abstract

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 α-subunit, a β-subunit that is important for enzyme activity, and a noncatalytic γ-subunit that binds AMP and activates the AMPK complex. We generated a skeletal muscle Cre-inducible transgenic mouse model expressing a mutant γ1-subunit (AMPKγ1(H151R)), resulting in chronic AMPK activation. The expression of the predominant AMPKγ3 isoform in skeletal muscle was reduced in extensor digitorum longus (EDL) muscle (81-83%) of AMPKγ1(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 AMPKγ1(H151R) transgenic mice. Furthermore, perigonadal white adipose tissue mass and serum leptin were reduced in female AMPKγ1(H151R) transgenic mice by 38 and 51% respectively. Conversely, in male AMPKγ1(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 AMPKγ1 in this model plays an important sex-specific role in skeletal muscle metabolism and whole body energy homeostasis.

KEYWORDS:

AMP-activated protein kinase; metabolism; skeletal muscle

PMID:
26306597
PMCID:
PMC4593773
DOI:
10.1152/ajpendo.00195.2015
[Indexed for MEDLINE]
Free PMC Article

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