Short-term, high-fat diet accelerates disuse @entity194 and protein degradation in a muscle-specific manner in XXXX .

@entity19 @entity2057 @entity194 @entity22227
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 @entity194 signals. The purpose of this study was to determine whether rapid weigh gain induced by a high-fat (HF) diet accelerates denervation-induced @entity2057 . METHODS: Adult, male @entity19 (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 @entity22227 , ubiquitination, myosin heavy chain (MHC) distribution, and mitochondrial subunits. RESULTS: When @entity19 were fed the 3wHF diet, whole-body fat mass more than doubled, but basal (innervated) muscle weights, rates of protein degradation, @entity22227 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 @entity22227 II, and the amount of overall ubiquitination as compared to the control fed @entity19 . On the contrary, the 3wHF diet had no significant effect in the EDL on amount of mass loss, proteolysis rate, @entity22227 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 @entity2057 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 @entity2057 .
