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Energy sensing pathways differentially regulate peroxisomes in skeletal muscle vs. liver
Author(s) -
Fuller Scott E.,
Worsham Emily A.,
Simon Jacob,
Gettys Thomas W.,
Mynatt Randall L.,
Noland Robert C.
Publication year - 2016
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.30.1_supplement.1246.2
Subject(s) - peroxisome , skeletal muscle , biology , ampk , microbiology and biotechnology , myogenesis , endocrinology , beta oxidation , lipotoxicity , medicine , insulin resistance , biochemistry , receptor , metabolism , protein kinase a , insulin , phosphorylation
Peroxisomes in skeletal muscle have the potential to combat lipid‐induced insulin resistance by providing an alternate route for lipid disposal which could reduce buildup of lipotoxic species while concomitantly limiting mitochondrial lipid overload. While much is known about regulation of peroxisomes in liver, there is limited information defining regulation of peroxisomes in skeletal muscle. These studies were designed to gain an understanding of peroxisomal regulation in skeletal muscle. Results indicate peroxisomes in rodent skeletal muscle were virtually unresponsive to ‘traditional’ stimuli that induce peroxisome proliferation in liver, such as peroxisome proliferator‐activated receptor (PPAR) agonists and lipid exposure. Alternatively, peroxisomal markers increased in skeletal muscle in response to dietary methionine restriction and caloric restriction. Interestingly, this response was specific to skeletal muscle as peroxisomal markers in the liver were decreased in response to these dietary manipulations. Since many beneficial effects incurred by caloric restriction are reported to be mediated via activation of energy sensing pathways, we further examined whether AMPK or sirtuin 1 (Sirt1) mediate tissue‐specific peroxisomal regulation. In support of this concept, pharmacological activation of AMPK (AICAR) and Sirt1 (resveratrol) enhanced peroxisomal genes in C2C12 myotubes, but decreased genes in AML‐12 hepatocytes. Initial findings point toward PGC1a as a potential downstream integration point mediating these effects in skeletal muscle. Overall, these findings support a model wherein skeletal muscle peroxisomes are uniquely responsive to energy status signals and interventions that activate these pathways, such as caloric restriction, exercise, cold exposure, etc., may mediate some of their therapeutic action via upregulation of peroxisomes in skeletal muscle. Support or Funding Information This work utilized the Genomics Core facilities at PBRC which is supported in part by COBRE (NIH 8 P20‐GM103528) and NORC (NIH 2P30‐DK072476) center grants from the National Institutes of Health. This research was also supported by NIH grants R01DK103860 (R.C.N.), R01DK089641 (R.L.M.), and a pilot and feasibility grant from NORC 2P30‐DK072476 (R.C.N.). Also, S.E.F. is supported by T32 fellowship NIH T32 AT004094.