Skeletal muscle myotubes in severe obesity exhibit altered ubiquitin-proteasome and autophagic/lysosomal proteolytic flux.

ABSTRACT: Whole-body protein metabolism is dysregulated with obesity. The goal of the study was to determine whether activity and expression of major protein degradation pathways are compromised specifically in human skeletal muscle with obesity.Primary human skeletal muscle (HSkM) cell cultures were utilized since cellular mechanisms can be studied absent of hormones and contractile activity that could independently influence metabolism. HSkM from 10 lean women (BMI???26.0 kg/m(2) ) and 8 women with severe obesity (BMI???39.0) were examined basally and when stimulated to atrophy (serum and amino acid starvation).HSkM from obese donors had a lower proportion of type I myosin heavy chain and slower flux through the autophagic/lysosomal pathway. During starvation, flux through the ubiquitin-proteasome system diverged according to obesity status, with a decrease in lean subjects and an increase in HSkM from subjects with obesity. HSkM in obesity also displayed elevated proteasome activity despite no difference in proteasome content. Atrophy-related gene expression and myotube area were similar in myotubes derived from individuals with and without obesity under basal and starved conditions.Our data indicate that muscle cells in lean individuals and in those with severe obesity have innate differences in management of protein degradation, which may explain their metabolic differences.

SUBMITTER: Bollinger LM 

PROVIDER: S-EPMC4445474 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature