Abstract
Dyslipidemia is commonly linked to skeletal muscle dysfunction, accumulation of intramyocellular lipids, and insulin resistance. However, our previous research indicated that dyslipidemia in apolipoprotein E and low-density lipoprotein receptor double knock-out mice (ApoE/LDLR -/-) leads to improvement of exercise capacity. This study aimed to investigate in detail skeletal muscle function and metabolism in these dyslipidemic mice. We found that ApoE/LDLR -/- mice showed an increased grip strength as well as increased troponins, and Mhc2 levels in skeletal muscle. It was accompanied by the increased skeletal muscle mitochondria numbers (judged by increased citrate synthase activity) and elevated total adenine nucleotides pool. We noted increased triglycerides contents in skeletal muscles and increased serum free fatty acids (FFA) levels in ApoE/LDLR -/- mice. Importantly, Ranolazine mediated inhibition of FFA oxidation in ApoE/LDLR -/- mice led to the reduction of exercise capacity and total adenine nucleotides pool. Thus, this study demonstrated that increased capacity for fatty acid oxidation, an adaptive response to dyslipidemia leads to improved cellular energetics that translates to increased skeletal muscle strength and contributes to increased exercise capacity in ApoE/LDLR -/- mice.
Highlights
Skeletal muscle is a heterogenic, dynamic, and flexible structure that is based on the arrangement of muscle fibers and associated connective tissue [1]
The step of our research was the examination of proteins levels characteristic for fast: troponin I type 2 and myosin heavy chain 2, as well as for slow skeletal muscle such as troponin I type I
There were no significant changes in troponins (Type I 1 and 2) and myosin heavy chain 2 degrees in skeletal muscles of LDLR -/- relative to control mice (Figure 2C–E)
Summary
Skeletal muscle is a heterogenic, dynamic, and flexible structure that is based on the arrangement of muscle fibers and associated connective tissue [1]. Muscle fibers are characterized by significant variability in the biochemical, mechanical, and metabolic phenotypes. The presence of fibers with different properties in the same muscle may reflect an adaptation to distinctive patterns of physical activity or genetic and metabolic diversity [1]. The most frequently used classification revealed the existence of four fiber types in mammalian skeletal muscles identified by the presence of specific myosin heavy chain isoforms: mitochondria-rich slow type 1 fiber, mitochondria-rich fast 2A, and 2X fibers, and mitochondria-poor fast 2B fibers [4,5]. Different types of muscle were characterized by the specific distribution of the two mitochondrial isocitrate dehydrogenases, IDH2 and IDH3 [6]
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