JCI - MAPK phosphatase-1 facilitates the loss of oxidative myofibers associated with obesity in mice

MAPK phosphatase-1 facilitates the loss of oxidative myofibers associated with obesity in mice

Rachel J. Roth, Annie M. Le, Lei Zhang, Mario Kahn, Varman T. Samuel, Gerald I. Shulman, Anton M. Bennett

Published in Volume 119, Issue 12

J Clin Invest. 2009; 119(12):3817–3829 doi:10.1172/JCI39054

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Figure 7

Enhanced PGC-1α expression and phosphorylation in mkp-1^–/– mice.

(A) Nuclear extracts of TA muscle from age-matched mkp-1^+/+ and mkp-1^–/– mice fed chow or HFD for 16 weeks were immunoblotted for phospho–p38 MAPK or p38 MAPK. Also shown are densitometric measurements for phospho–p38 MAPK levels normalized to total p38 MAPK. Data are mean ± SEM (n = 8–9). (B) Nuclear extracts as in A were immunoblotted for phospho-Ser265 PGC-1α. Lanes were run on the same gel but were noncontiguous (white line). Also shown are densitometric measurements for phospho-Ser265 PGC-1α expression normalized to Lamin-β1. Data are mean ± SEM (n = 4–9). (C) TA muscle was isolated from mkp-1^+/+ and mkp-1^–/– mice fed chow or HFD for 16 weeks. Muscle lysates were immunoblotted with PGC-1α antibodies, and densitometric measurements for PGC-1α expression were normalized to p38 MAPK. Data are mean ± SEM (n = 6). (D) Under HFD conditions, exposure to FAs increases MKP-1 expression, causing inactivation of nuclear p38 MAPK. Reduced p38 MAPK–mediated phosphorylation of PGC-1α decreases PGC-1α expression. Impaired skeletal muscle PGC-1α function facilitates loss of oxidative myofiber composition. ^‡P = 0.05; *P < 0.05; **P < 0.005.