Short‐term high‐fat feeding induces muscle‐type–specific signaling adaptations in skeletal muscle of male rats

Short-term high-fat diet (HFD) feeding is used to study metabolic dysregulation, yet many rodent models use extreme fat contents that may not reflect physiological conditions. Skeletal muscle responses to short-term HFD also vary by muscle type. We tested whether a physiologically relevant HFD induces muscle-type-specific changes in skeletal muscle signaling and mitochondrial-related proteins. Male Wistar rats were fed a low-fat diet (LFD; 10% energy from fat) or HFD (40% energy from fat) for 4 weeks (n = 5/group). Soleus and extensor digitorum longus (EDL) muscles were analyzed for OXPHOS complexes, mitochondrial dynamics proteins, and ERK1/2 signaling. HFD increased energy intake and visceral adiposity without changing body weight or muscle mass. In soleus, OXPHOS complex II was reduced, whereas other complexes were preserved. In EDL, phosphorylation of ERK1/2 (Thr202/Tyr204) and Drp1 (Ser616) was reduced without changes in total protein abundance. Thus, short-term, physiologically relevant HFD feeding induces muscle-type-specific molecular and signaling adaptations before overt changes in body weight or muscle mass.