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

Abstract

In this study, we investigated the effects of a short‐term and long‐term high‐fat diet (HFD) on morphological and functional features of fast‐twitch skeletal muscle. Male C57BL/6J mice were fed a HFD (60% fat) for 4 weeks (4‐week HFD) or 12 weeks (12‐week HFD). Subsequently, the fast‐twitch extensor digitorum longus muscle was isolated, and the composition of muscle fiber type, expression levels of proteins involved in muscle contraction, and force production on electrical stimulation were analyzed. The 12‐week HFD, but not the 4‐week HFD, resulted in a decreased muscle tetanic force on 100 Hz stimulation compared with control (5.1 ± 1.4 N/g in the 12‐week HFD vs. 7.5 ± 1.7 N/g in the control group; P < 0.05), whereas muscle weight and cross‐sectional area were not altered after both HFD protocols. Morphological analysis indicated that the percentage of type IIx myosin heavy chain fibers, mitochondrial oxidative enzyme activity, and intramyocellular lipid levels increased in the 12‐week HFD group, but not in the 4‐week HFD group, compared with controls (P < 0.05). No changes in the expression levels of calcium handling‐related proteins and myofibrillar proteins (myosin heavy chain and actin) were detected in the HFD models, whereas fast‐troponin T‐protein expression was decreased in the 12‐week HFD group, but not in the 4‐week HFD group (P < 0.05). These findings indicate that a long‐term HFD, but not a short‐term HFD, impairs contractile force in fast‐twitch muscle fibers. Given that skeletal muscle strength largely depends on muscle fiber type, the impaired muscle contractile force by a HFD might result from morphological changes of fiber type composition.

The impact of a high-fat diet in mice is dependent on duration and age, and differs between muscles

“…In line with previous studies (Andrich et al, 2018;Baek et al, 2018;Eshima et al, 2017;Hegarty et al, 2002;Kaneko et al, 2011;Silvennoinen et al, 2013), this was accompanied by elevated IMCL levels in the soleus, diaphragm and EDL of our mice. This HFD-induced increase in body mass, BMI and IMCL occurred after only 9 weeks in old mice, but was only seen after 16 weeks in the young-adult mice, similar to the absence of changes in IMCL after 4 weeks and elevated IMCL levels after 12 weeks of a HFD seen by others in young-adult mice (Eshima et al, 2017). It should be noted, however, that the BMI of the control old mice was higher than that of the young-adult mice, suggesting greater adiposity.…”

“…However, several studies in humans and rodents showed an increase in oxidative capacity with HFD (Garcia-Roves et al, 2006;Hancock et al, 2008;Iossa et al, 2002;Li et al, 2016a;Miller et al, 1984;Sadler et al, 2012), rather than a decrease. This discrepancy may be due to differences in diet duration as the effects of a HFD are time dependent: a 4 week period of HFD resulted in little effect on the extensor digitorum longus (EDL) oxidative capacity, but a significant increase after a 12 week period (Eshima et al, 2017). In addition, adaptations to a HFD may be muscle specific and dependent on age.…”

“…The majority of current available data on the effects of a HFD on skeletal muscle morphology do not consider aged animals (Bonnard et al, 2008;de Wilde et al, 2008;Eshima et al, 2017;Nwadozi et al, 2016;Silvennoinen et al, 2013). However, one study that examined the effect of an extended HFD on in vivo skeletal muscle morphology and lipid content in aged rats reported an inverse association between hindlimb muscle volume and muscular lipid content (Bollheimer et al, 2012).…”

High-fat diet suppresses the positive effect of creatine supplementation on skeletal muscle function by reducing protein expression of IGF-PI3K-AKT-mTOR pathway

“…In comparison to SD, our data from the HF group initially suggested an increase of maximal carrying load and total isotonic force; however, once these parameters were normalized to the body weight, rats from the SD group were able to carry significantly more load than those from the HF group, with no difference in total isotonic force (Fig 4). These results are supported by the inverse relationship between fiber size and loss in force generation capacity in in vitro muscle fibers in obese older mice [40, 41]. Moreover, our protein level expression analyses suggested that HF diet significantly reduced main targets of the protein synthesis in almost the entire IGF1-IRS1-PI3K-AKT-mTOR pathway (Fig 6).…”

“…Moreover, by comparing SD-T-CrM and HF-T-CrM data normalized to body weight (Fig 5), we observed that diet has a crucial effect on muscle performance. Long-term HF diet changes muscle fiber-type and myofibers inhibiting thus the CrM and resistance training effects on muscle contractile force [41]. Once we evaluated the protein expression, we observed a similar protein expression of HF-T-CrM in comparison to HF-T group, with the interesting difference that the HF-CrM group showed significantly reduced protein levels of phospho-AKT and S6K.…”