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Ob/Ob Mice But Not High Fat Fed Mice Exhibit Divergent Changes in Atrogin‐1 and Bnip3 Expression in Skeletal Muscle
Author(s) -
Gaugler Megan,
Reynolds Thomas H.
Publication year - 2010
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.24.1_supplement.597.2
Subject(s) - endocrinology , medicine , skeletal muscle , autophagy , ubiquitin , muscle atrophy , messenger rna , blot , proteolysis , atrophy , insulin resistance , protein degradation , type 2 diabetes , diabetes mellitus , chemistry , biology , gene , apoptosis , biochemistry , enzyme
The purpose of this study was to determine whether diet‐induced insulin resistance and type 2 diabetes are associated with an increase in the expression of the muscle atrophy related genes atrogin‐1 and Bnip3. Mice were fed a high fat diet (HFD) or a normal chow (CON) diet for 8 months. Following the dietary intervention muscles were removed and processed for immuno‐blotting or quantitative polymerase chain reaction (qPCR) experiments to assess atrogin‐1 and Bnip3 protein and mRNA levels, respectively. We observed no effect of the high fat diet on atrogin‐1 and Bnip3 protein levels or mRNA levels. These results indicate that long‐term high fat diet interventions do not activate ubiquitin‐dependent protein degradation and/or autophagy. Identical experiments were conducted with muscles from genetically obese (Ob/Ob) mice. There was a significant decline in atrogin‐1 protein levels in muscles from Ob/Ob mice compared to CON mice. Furthermore, a trend existed for higher levels of Bnip3 expression in muscles from Ob/Ob mice (P = 0.078). These results suggest that the loss of muscle mass with severe type 2 diabetes is due, in part, to increased autophagy rather than ubiquitin mediated proteolysis. Alternative, a decline in atrogin‐1 levels in muscles from type 2 diabetics may lead to an accumulation of damage proteins resulting in skeletal muscle contractile dysfunction.