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

Abstract

High-fat (HF) diets in combination with sedentary lifestyle represent one of the major public health concerns predisposing to obesity and diabetes leading to skeletal muscle atrophy, decreased fiber diameter and muscle mass with accumulation of fat tissue resulting in loss of muscle strength. One strategy to overcome the maleficent effects of HF diet is resistance training, a strategy used to improve muscle mass, reverting the negative effects on obesity-related changes in skeletal muscle. Together with resistance training, supplementation with creatine monohydrate (CrM) in the diet has been used to improve muscle mass and strength. Creatine is a non-essential amino acid that is directly involved in the cross-bridge cycle providing a phosphate group to ADP during the initiation of muscle contraction. Besides its antioxidant and anti-inflammatory effects CrM also upregulates IGF-1 resulting in hyperthophy with an increase in muscle function. However, it is unknown whether CrM supplementation during resistance training would revert the negative effects of high-fat diet on the muscle performance. During 8 weeks we measured muscle performance to climb a 1.1m and 80° ladder with increasing load on trained rats that had received standard diet or high-fat diet, supplemented or not with CrM. We observed that the CrM supplementation up-regulated IGF-1 and phospho-AKT protein levels, suggesting an activation of the IGF1-PI3K-Akt/PKB-mTOR pathway. Moreover, despite the CrM supplementation, HF diet down-regulated several proteins of the IGF1-PI3K-Akt/PKB-mTOR pathway, suggesting that diet lipid content is crucial to maintain or improve muscle function during resistance training.

Changes in UPR-PERK pathway and muscle hypertrophy following resistance training and creatine supplementation in rats

“…In line with the current results, Ferretti et al [10] reported that Cr supplementation combined with 8 week ladder climbing training increased the phosphorylated AKT and phospho-AKT/total AKT, but had no effect on the mTOR and phospho-mTOR/total mTOR. Aguiar et al [1] investigated the effect of Cr supplementation and 5 weeks of a resistance training program (5 d/wk) on muscle hypertrophy in an animal model.…”

“…It has been reported that amino acid transporter expression following resistance exercise might be linked to mTOR signaling and eIF2α phosphorylation [8]. On the other hand, Cr supplementation in addition to resistance training increases the diameter of skeletal muscle bers by stimulating the expression of insulin-like growth factor-1 (IGF-1) and subsequently activating the AKT-mTOR pathway [10]. Given that both PERK and mTOR are involved in protein synthesis, skeletal muscle mass [23] and satellite cell homeostasis [36], there is limited information regarding the effect of resistance training-induced hypertrophy on PERK pathway.…”

Omega-3 Fatty Acids-Enriched Fish Oil Activates AMPK/PGC-1α Signaling and Prevents Obesity-Related Skeletal Muscle Wasting

“…In addition, Eshima et al discovered morphological changes of myofiber composition of extensor digitorum longus muscle in HF diet-fed mice for 12 weeks, leading to the impairment of muscle contractile force [17]. Moreover, the mechanisms of skeletal muscle wasting and dysfunction in HF diet-induced obesity are positively correlated among several risk factors and signaling pathways including cardiometabolic risk factors [18], elevating inflammatory factors (such as tumor necrosis factor-α (TNF-α) levels), the activation of oxidative stress [5], autophagy [19,20], and ubiquitin–proteasome pathway [5], the down-regulation of AMPK/PGC-1 [21,22] and IGF/PI3K/Akt/mTOR signaling pathway [21,23], leading to skeletal muscle atrophy and apoptosis.…”

“…A Nikon Eclipse TS100 microscope equipped with a Nikon D5100 digital camera was used to observe and photograph the H&E-stained sections. The cross-section areas (CSA) of individual myofibres were counted and calculated using the image J 1.48 software (National Institutes of Health, Bethesda, MD, USA) in five random fields of each section, as described previously [23,54].…”

Efficacy of Nutritional Interventions as Stand-Alone or Synergistic Treatments with Exercise for the Management of Sarcopenia

“…This positive effect of creatine on muscle is probably only observable together with exercise [135,136,137]. Just recently, Ferretti et al [138] demonstrated that during resistance training, Cr monohydrate increases muscle size and performance, suggesting a higher activation of muscle protein synthesis via IGF1-IRS1-PI3K-AKT-mTOR pathway.…”