Early oxidative shifts in mouse skeletal muscle morphology with high-fat diet consumption do not lead to functional improvements

Abstract

Short‐term consumption of a high‐fat diet (HFD) can result in an oxidative shift in adult skeletal muscle. However, the impact of HFD on young, growing muscle is largely unknown. Thus, 4‐week‐old mice were randomly divided into sedentary HFD (60% kcal from fat), sedentary standard chow (control), or exercise‐trained standard chow. Tibialis anterior (TA) and soleus muscles were examined for morphological and functional changes after 3 weeks. HFD consumption increased body and epididymal fat mass and induced whole body glucose intolerance versus control mice. Compared to controls, both HFD and exercise‐trained TA muscles displayed a greater proportion of oxidative fibers and a trend for an increased succinate dehydrogenase (SDH) content. The soleus also displayed an oxidative shift with increased SDH content in HFD mice. Despite the aforementioned changes, palmitate oxidation rates were not different between groups. To determine if the adaptive changes with HFD manifest as a functional improvement, all groups performed pre‐ and postexperiment aerobic exercise tests. As expected, exercise‐trained mice improved significantly compared to controls, however, no improvement was observed in HFD mice. Interestingly, capillary density was lower in HFD muscles; a finding which may contribute to the lack of functional differences seen with HFD despite the oxidative shift in skeletal muscle morphology. Taken together, our data demonstrate that young, growing muscle exhibits early oxidative shifts in response to a HFD, but these changes do not translate to functional benefits in palmitate oxidation, muscle fatigue resistance, or whole body exercise capacity.

Long-term, but not short-term high-fat diet induces fiber composition changes and impaired contractile force in mouse fast-twitch skeletal muscle

“…These oxidative changes after a HFD have been reported in a previous study (Thomas et al. ), but the change did not result in functional benefits in muscle fatigue resistance, or whole body exercise capacity (Thomas et al. ).…”

“…; Thomas et al. ; Mastrocola et al. ), we observed an increased percentage of type IIx fibers as a result of a decrease in type IIb fibers in EDL muscle in long‐term HFD‐fed mice, but these changes were not observed in short‐term HFD‐fed mice (Fig.…”

“…; Thomas et al. ). Consistently, we found that a short‐term HFD (4 week) did not significantly alter contractile force (Fig.…”

“…For example, mice fed a HFD for 3 weeks (Thomas et al. ) or 8 weeks (Shortreed et al. ) did not have significant impairment of the contractile force of fast‐twitch dominant muscles.…”

Muscle Arnt/Hif1β Is Dispensable in Myofiber Type Determination, Vascularization and Insulin Sensitivity

“…However, even under HFD feeding conditions, lack of muscle ARNT expression does not impact the aforementioned adaptation or as such change myofiber type composition, oxidative capacity, mitochondrial content, weight gain and insulin tolerance. The effect of HFD feeding on muscle capillarity in mice is unclear, as in one study HFD caused muscle capillary regression in mice [33]; whereas, in another it increased angiogenesis and capillarity, without affecting HIF1 expression [34]. Nevertheless, ARNT deletion did not affect capillary density at least in the skeletal muscles of NCD-fed mice, which was somewhat surprising given the central role for HIF1 in regulating angiogenesis.…”