Diets High in Sugar, Fat, and Energy Induce Muscle Type–Specific Adaptations in Mitochondrial Functions in Rats

Abstract

Obesity is often associated with insulin resistance and mitochondrial dysfunction within skeletal muscles, but the causative factors are not clearly identified. The present study examined the role of nutrition, both qualitatively and quantitatively, in the induction of muscle mitochondrial defects. Two experimental diets [high sucrose (SU) and high fat (F)] were provided for 6 wk to male Wistar rats at 2 levels of energy [standard (N) and high (H)] and compared with a standard energy cornstarch-based diet (C). Insulin sensitivity (intraperitoneal glucose tolerance test, IPGTT) and intramyocellular triglyceride (IMTG) content (1H MRS) were determined at wk 5. Mitochondrial oxidative phosphorylation and superoxide anion radical (MSR) production were assessed on soleus (oxidative) and tibialis (glycolytic) muscles. Experimental diets induced hyperinsulinemia during IPGTT (P < 0.01 vs. C). Rats in the HSU and HF groups were hyperglycemic relative to the C group, P < 0.05 vs. C. The severity of insulin resistance paralleled IMTG accumulation (P < 0.05). In soleus, mitochondrial respiration and ATP production rates were lower in HSU and HF than in C (P < 0.05). By contrast, respiration was unaffected by the diets in tibialis, whereas ATP production tended to be lower in rats fed the experimental diets compared with C (P = 0.09). Mitochondrial adaptations were associated with more than a 50% reduction in MSR production in HSU and HF compared with C in both soleus (P < 0.05) and tibialis (P < 0.01). Changes in mitochondrial functions in the NSU and NF groups were intermediate and not significantly different from C. Therefore, excess fat or sucrose and more importantly, excess energy intake by rats is associated with muscle type-specific mitochondrial adaptations, which contribute to decrease mitochondrial production of ATP and reactive oxygen species.

A reciprocal interaction between food-motivated behavior and diet-induced obesity

“…38 There is, however, evidence that a high-sucrose diet changes glucose utilization by changing insulin sensitivity especially in the muscle. 39 Whether our HFHS-choice diet changes glucose utilization remains to be determined.…”

Skeletal muscle insulin resistance: role of mitochondria and other ROS sources

“…The results obtained in these animal models are mostly in agreement with those obtained in human studies. The most used protocol to induce insulin resistance is overfeeding with high-fat/high-sugar diets in rats (Chanseaume et al 2006, Gomes et al 2012, Crescenzo et al 2013, Warren et al 2014 or 233:1 in mice (de Wilde et al 2008, Shelley et al 2009, Yuzefovych et al 2013, however, models of genetic obesity were also used (Holmström et al 2012). However, other observations report discrepant results, showing that high-fat feeding in rats was associated with no variation (Atgié et al 1993, De Feyter et al 2008a or even a higher mitochondrial capacity (Hancock et al 2008), and IR could be related to incomplete intramitochondrial β-oxidation (Koves et al 2008).…”

MECHANISMS IN ENDOCRINOLOGY: Skeletal muscle lipotoxicity in insulin resistance and type 2 diabetes: a causal mechanism or an innocent bystander?

“…Conversely, infusion of lipids decreases expression of PGC1α and nuclear-encoded mitochondrial genes (93), and experimental high-fat feeding in healthy humans also results in decreased PGC1α and mitochondrial gene expression in skeletal muscle only after 3 days (89). Interestingly, high-fat and/or hypercaloric diets have been shown to promote alterations in mitochondrial oxidative phosphorylation (OXPHOS) activity and to decrease PGC1α gene expression (90,94). Impaired OXPHOS gene expression is anticipated to lower the capacity of the cell to handle substrate in excess, which could also contribute to exhaustion of mitochondria during longer periods of high energy intake.…”