title: Short-term, high-fat diet accelerates disuse atrophy and protein degradation in a muscle-specific manner in mice.
abstract: BACKGROUND
  A short-term high-fat diet impairs mitochondrial function and the ability of skeletal muscle to respond to growth stimuli, but it is unknown whether such a diet alters the ability to respond to atrophy signals. The purpose of this study was to determine whether rapid weigh gain induced by a high-fat (HF) diet accelerates denervation-induced muscle atrophy.
  
  
  METHODS
  Adult, male mice (C57BL/6) were fed a control or HF (60 % calories as fat) diet for 3 weeks (3wHF). Sciatic nerve was sectioned unilaterally for the final 5 or 14 days of the diet. Soleus and extensor digitorum longus (EDL) muscles were removed and incubated in vitro to determine rates of protein degradation and subsequently homogenized for determination of protein levels of LC3, ubiquitination, myosin heavy chain (MHC) distribution, and mitochondrial subunits.
  
  
  RESULTS
  When mice were fed the 3wHF diet, whole-body fat mass more than doubled, but basal (innervated) muscle weights, rates of protein degradation, LC3 content, mitochondrial protein content, and myosin isoform distribution were not significantly different than with the control diet in either soleus or EDL. However in the 14 day denervated soleus, the 3wHF diet significantly augmented loss of mass, proteolysis rate, amount of the autophagosome marker LC3 II, and the amount of overall ubiquitination as compared to the control fed mice. On the contrary, the 3wHF diet had no significant effect in the EDL on amount of mass loss, proteolysis rate, LC3 levels, or ubiquitination. Fourteen days denervation also induced a loss of mitochondrial proteins in the soleus but not the EDL, regardless of the diet.
  
  
  CONCLUSIONS
  Taken together, a short-term, high-fat diet augments denervation muscle atrophy by induction of protein degradation in the mitochondria-rich soleus but not in the glycolytic EDL. These findings suggest that the denervation-induced loss of mitochondria and HF diet-induced impairment of mitochondrial function may combine to promote skeletal muscle atrophy.
authors.affiliation: East Carolina Diabetes and Obesity Institute, East Carolina University, Greenville, NC USA ; Human Performance Lab, Department of Kinesiology, College of Health and Human Performance, East Carolina University, Greenville, NC USA.
authors.forename: Steven L
authors.initials: SL
authors.lastname: Roseno
authors.affiliation: East Carolina Diabetes and Obesity Institute, East Carolina University, Greenville, NC USA ; Human Performance Lab, Department of Kinesiology, College of Health and Human Performance, East Carolina University, Greenville, NC USA.
authors.forename: Patrick R
authors.initials: PR
authors.lastname: Davis
authors.affiliation: Department of Kinesiology and Health Promotion, College of Education, University of Kentucky, Lexington, KY USA.
authors.forename: Lance M
authors.initials: LM
authors.lastname: Bollinger
authors.affiliation: East Carolina Diabetes and Obesity Institute, East Carolina University, Greenville, NC USA ; Human Performance Lab, Department of Kinesiology, College of Health and Human Performance, East Carolina University, Greenville, NC USA.
authors.forename: Jonathan J S
authors.initials: JJ
authors.lastname: Powell
authors.affiliation: East Carolina Diabetes and Obesity Institute, East Carolina University, Greenville, NC USA ; Human Performance Lab, Department of Kinesiology, College of Health and Human Performance, East Carolina University, Greenville, NC USA ; Department of Physiology, Brody School of Medicine, East Carolina University, Greenville, 27834 NC USA ; Department of Biochemistry and Molecular Biology, Brody School of Medicine, East Carolina University, Greenville, NC USA.
authors.forename: Carol A
authors.initials: CA
authors.lastname: Witczak
authors.affiliation: East Carolina Diabetes and Obesity Institute, East Carolina University, Greenville, NC USA ; Human Performance Lab, Department of Kinesiology, College of Health and Human Performance, East Carolina University, Greenville, NC USA ; Department of Physiology, Brody School of Medicine, East Carolina University, Greenville, 27834 NC USA ; Department of Biochemistry and Molecular Biology, Brody School of Medicine, East Carolina University, Greenville, NC USA.
authors.forename: Jeffrey J
authors.identifier: 0000-0003-3503-0528
authors.initials: JJ
authors.lastname: Brault
keywords: Muscular atrophy; Obesity; Skeletal muscle