Muscle-Specific Adaptations, Impaired Oxidative Capacity and Maintenance of Contractile Function Characterize Diet-Induced Obese Mouse Skeletal Muscle

Abstract

BackgroundThe effects of diet-induced obesity on skeletal muscle function are largely unknown, particularly as it relates to changes in oxidative metabolism and morphology.Principal FindingsCompared to control fed mice, mice fed a high fat diet (HFD; 60% kcal: fat) for 8 weeks displayed increased body mass and insulin resistance without overt fasting hyperglycemia (i.e. pre-diabetic). Histological analysis revealed a greater oxidative potential in the HFD gastrocnemius/plantaris (increased IIA, reduced IIB fiber-type percentages) and soleus (increased I, IIA cross-sectional areas) muscles, but no change in fiber type percentages in tibialis anterior muscles compared to controls. Intramyocellular lipid levels were significantly increased relative to control in HFD gastrocnemius/plantaris, but were similar to control values in the HFD soleus. Using a novel, single muscle fiber approach, impairments in complete palmitate and glucose oxidation (72.8±6.6% and 61.8±9.1% of control, respectively; p<0.05) with HFD were detected. These reductions were consistent with measures made using intact extensor digitorum longus and soleus muscles. Compared to controls, no difference in succinate dehydrogenase or citrate synthase enzyme activities were observed between groups in any muscle studied, however, short-chain fatty acyl CoA dehydrogenase (SCHAD) activity was elevated in the HFD soleus, but not tibialis anterior muscles. Despite these morphological and metabolic alterations, no significant difference in peak tetanic force or low-frequency fatigue rates were observed between groups.ConclusionsThese findings indicate that HFD induces early adaptive responses that occur in a muscle-specific pattern, but are insufficient to prevent impairments in oxidative metabolism with continued high-fat feeding. Moreover, the morphological and metabolic changes which occur with 8 weeks of HFD do not significantly impact muscle contractile properties.

Increased intramyocellular lipids but unaltered in vivo mitochondrial oxidative phosphorylation in skeletal muscle of adipose triglyceride lipase-deficient mice

“…Changes in muscle fiber type composition can occur in response to skeletal muscle lipid surplus (49). However, this was not observed in the TA muscle of ATGL Ϫ/Ϫ mice.…”

Skeletal Muscle Gene Expression Profile Is Modified by Dietary Protein Source and Calcium during Energy Restriction

“…Under normal situations, leptin is known to improve insulin sensitivity in skeletal muscles by stimulating fatty acid oxidation and by decreasing the lipid content [21]. It is known that a high-fat diet increases the intramyocellular lipid level and impairs the skeletal muscle oxidative capacity [ [22,23], for reviews see ref. [24,25]].…”

Oligomeric Cocoa Procyanidins Possess Enhanced Bioactivity Compared to Monomeric and Polymeric Cocoa Procyanidins for Preventing the Development of Obesity, Insulin Resistance, and Impaired Glucose Tolerance during High-Fat Feeding

“…Even fewer are studies that have sought to define the structure-function relationship of these flavanols on the body. In this chapter, a mouse model was used in which lean mice were fed a HF diet containing 60% kcal from fat to induce obesity, insulin resistance, and impaired glucose tolerance 116,117 . The CE and individual CPC fractions (monomer, oligomer, and polymer) that were generated in the previous chapter were incorporated into the HF diet, and the onset of obesity and T2D biomarkers were compared to a negative control (LF diet only), and a positive control (HF diet only).…”