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Muscle‐specific deletion of p38α/β MAPK improves glucose tolerance and reduces body fat but impairs exercise capacity
Author(s) -
Greene Nicholas Perry,
Lira Vitor A,
Chain Kristopher H,
Zhang Mei,
Hargett Stefan R,
Keller Susanna R,
Yan Zhen
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.1152.22
Subject(s) - skeletal muscle , endocrinology , medicine , mitochondrial biogenesis , insulin resistance , p38 mitogen activated protein kinases , protein kinase a , biology , insulin , kinase , function (biology) , microbiology and biotechnology
The p38 MAPK belong to the stress‐activated kinase family, and p38γ MAPK is vital to exercise‐induced PGC‐1α expression, mitochondrial biogenesis and angiogenesis in skeletal muscle. However, the roles of p38α and p38β in skeletal muscle remain unclear likely due to redundanct function. To determine the function of these isoforms in skeletal muscle, we generated muscle‐specific p38α/β double knockout mice (DMKO). We then subjected these mice to 12 weeks of 45% high‐fat diet (HFD). DMKO mice showed improved glucose tolerance compared with wild‐type (WT) littermates on normal chow and HFD. DMKO mice showed reductions in total body weight, and muscle and epididymal fat mass compared with WT mice, accompanied by increased energy expenditure at equivalent caloric consumption. DMKO mice showed reduced exercise capacity as assessed by treadmill running. These findings demonstrate protective effects of p38α/β MAPK deletion in skeletal muscle regarding the development of insulin resistance and gains in body weight and fat mass, associated with increased energy expenditure. However, p38α/β MAPK deletion impairs exercise capacity suggesting a critical role in muscle function that requires further examination.