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Skeletal Muscle Peroxisome Proliferator‐Activated Alpha is Differentially Regulated with Severe Obesity
Author(s) -
Cox Lauren,
Maples Jill,
Rowland Naomi,
Hubal Monica,
Houmard Joseph
Publication year - 2015
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.29.1_supplement.817.8
Subject(s) - endocrinology , peroxisome proliferator activated receptor , medicine , skeletal muscle , beta oxidation , epigenetics , lipid metabolism , peroxisome , downregulation and upregulation , dna methylation , peroxisome proliferator activated receptor alpha , biology , regulator , metabolic syndrome , gene expression , receptor , obesity , nuclear receptor , gene , biochemistry , metabolism , transcription factor
The skeletal muscle of severely obese individuals has an impaired ability to increase fatty acid oxidation (FAO) in response to dietary lipid, termed metabolic inflexibility. It is hypothesized metabolic inflexibility is associated with a failure to coordinately upregulate genes involved in FAO. While the molecular mechanisms contributing to metabolic inflexibility are not evident, a possible candidate is peroxisome proliferator‐activated receptor alpha (PPAR), which is a critical regulator of FAO. The present study was undertaken to determine if there is a differential response to lipid oversupply, in terms of PPARA mRNA and/or protein expression in skeletal muscle with severe obesity; potentially linked to epigenetic modifications (e.g. DNA methylation). In primary human skeletal muscle cultures (HSkMC) from lean and severely obese women, there was a significant (P<0.05) interaction effect in response to lipid treatment (48hr 1:1 oleate:palmitate) where mRNA content increased in the lipid‐treated state among the lean, but not the obese. This differential response in mRNA content was accompanied by lipid‐induced changes in CpG methylation within the PPARA gene. However, lipid‐induced differences between lean and obese women were not evident at the protein level. In terms of identifying mechanisms that contribute to the metabolic inflexibility with severe obesity, the transcriptional regulation of PPARA may play a role.