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

Objective 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. Methods Primary human skeletal muscle (HSkM) cell cul...

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Veröffentlicht in:Obesity (Silver Spring, Md.) Md.), 2015-06, Vol.23 (6), p.1185-1193
Hauptverfasser: Bollinger, Lance M., Powell, Jonathan J. S., Houmard, Joseph A., Witczak, Carol A., Brault, Jeffrey J.
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container_end_page 1193
container_issue 6
container_start_page 1185
container_title Obesity (Silver Spring, Md.)
container_volume 23
creator Bollinger, Lance M.
Powell, Jonathan J. S.
Houmard, Joseph A.
Witczak, Carol A.
Brault, Jeffrey J.
description Objective 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. Methods 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/m2) and 8 women with severe obesity (BMI ≥ 39.0) were examined basally and when stimulated to atrophy (serum and amino acid starvation). Results 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. Conclusions 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.
doi_str_mv 10.1002/oby.21081
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S. ; Houmard, Joseph A. ; Witczak, Carol A. ; Brault, Jeffrey J.</creator><creatorcontrib>Bollinger, Lance M. ; Powell, Jonathan J. S. ; Houmard, Joseph A. ; Witczak, Carol A. ; Brault, Jeffrey J.</creatorcontrib><description>Objective 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. Methods 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/m2) and 8 women with severe obesity (BMI ≥ 39.0) were examined basally and when stimulated to atrophy (serum and amino acid starvation). Results 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. Conclusions 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.</description><identifier>ISSN: 1930-7381</identifier><identifier>EISSN: 1930-739X</identifier><identifier>DOI: 10.1002/oby.21081</identifier><identifier>PMID: 26010327</identifier><language>eng</language><publisher>United States: Blackwell Publishing Ltd</publisher><subject>Adult ; Autophagy ; Biopsy ; Cell culture ; Cell Culture Techniques ; Enzymes ; Female ; Gene Expression ; Humans ; Insulin ; Insulin resistance ; Insulin-like growth factors ; Lysosomes - metabolism ; Metabolism ; Muscle Fibers, Skeletal - metabolism ; Muscle, Skeletal - metabolism ; Musculoskeletal system ; Obesity ; Obesity, Morbid - metabolism ; Proteasome Endopeptidase Complex - metabolism ; Protein synthesis ; Proteins ; Real-Time Polymerase Chain Reaction ; Studies ; Ubiquitin - metabolism ; Young Adult</subject><ispartof>Obesity (Silver Spring, Md.), 2015-06, Vol.23 (6), p.1185-1193</ispartof><rights>2015 The Obesity Society</rights><rights>2015 The Obesity Society.</rights><rights>Copyright Blackwell Publishing Ltd. 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HSkM from 10 lean women (BMI ≤ 26.0 kg/m2) and 8 women with severe obesity (BMI ≥ 39.0) were examined basally and when stimulated to atrophy (serum and amino acid starvation). Results 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. 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S.</creatorcontrib><creatorcontrib>Houmard, Joseph A.</creatorcontrib><creatorcontrib>Witczak, Carol A.</creatorcontrib><creatorcontrib>Brault, Jeffrey J.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Health &amp; Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><jtitle>Obesity (Silver Spring, Md.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Bollinger, Lance M.</au><au>Powell, Jonathan J. S.</au><au>Houmard, Joseph A.</au><au>Witczak, Carol A.</au><au>Brault, Jeffrey J.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Skeletal muscle myotubes in severe obesity exhibit altered ubiquitin‐proteasome and autophagic/lysosomal proteolytic flux</atitle><jtitle>Obesity (Silver Spring, Md.)</jtitle><addtitle>Obesity (Silver Spring)</addtitle><date>2015-06</date><risdate>2015</risdate><volume>23</volume><issue>6</issue><spage>1185</spage><epage>1193</epage><pages>1185-1193</pages><issn>1930-7381</issn><eissn>1930-739X</eissn><abstract>Objective 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. 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source MEDLINE; Access via Wiley Online Library; Wiley Online Library (Open Access Collection)
subjects Adult
Autophagy
Biopsy
Cell culture
Cell Culture Techniques
Enzymes
Female
Gene Expression
Humans
Insulin
Insulin resistance
Insulin-like growth factors
Lysosomes - metabolism
Metabolism
Muscle Fibers, Skeletal - metabolism
Muscle, Skeletal - metabolism
Musculoskeletal system
Obesity
Obesity, Morbid - metabolism
Proteasome Endopeptidase Complex - metabolism
Protein synthesis
Proteins
Real-Time Polymerase Chain Reaction
Studies
Ubiquitin - metabolism
Young Adult
title Skeletal muscle myotubes in severe obesity exhibit altered ubiquitin‐proteasome and autophagic/lysosomal proteolytic flux
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