Current information regarding the effects of a high-fat diet (HFD) on skeletal muscle is contradictory. This study aimed to investigate the effects of a long-term HFD on skeletal muscle in male and female mice at the morphological, cellular, and molecular levels. Adult mice of the C57BL/6 strain were fed standard chow or an HFD for 20 weeks. The tibialis anterior muscles were dissected, weighed, and processed for cellular and molecular analyses. Immunocytochemical and morphometric techniques were applied to quantify fiber size, satellite cells (SCs), and myonuclei. Additionally, PCR array and RT-qPCR tests were performed to determine the expression levels of key muscle genes. Muscles from HFD mice showed decreases in weight, SCs, and myonuclei, consistent with the atrophic phenotype. This atrophy was associated with a decrease in the percentage of oxidative fibers within the muscle. These findings were further confirmed by molecular analyses that showed significant reductions in the expression of Pax7, Myh1, and Myh2 genes and increased Mstn gene expression. Male and female mice showed similar trends in response to HFD-induced obesity. These findings indicate that the long-term effects of obesity on skeletal muscle resemble those of age-related sarcopenia.
High‐Fat Diet (HFD) affects the skeletal muscle fibers at both morphological and functional levels. At a functional level, it has been reported that HFD reduces the oxidative capacity and leads to insulin resistance in the skeletal muscle tissue. However, there are very limited and conflicting information about the effects of HFD on the morphology of skeletal muscle fibers. This study aimed to clarify the effects of long‐term feeding with HFD on murine skeletal muscle fibers. These effects include the size of skeletal muscle fibers, frequency of satellite cells, and number of myonuclei within the fibers. Adult male mice of the C57BL/6 strain were randomly divided into 2 groups; a control group, and a HFD group. Each group contained four mice. Food and water were provided ad libitum. At the end of a twenty‐week feeding period, the tibialis anterior (TA) muscle was dissected out from each animal and weighed. Immunocytochemical and morphometric image analyses techniques were applied to quantify the fiber diameter, satellite cell frequency, and number of myonuclei per fiber cross‐section. The HFD group showed a significant (P<0.01) decrease in TA muscle weight compared to control group. However, a significant (P<0.05) increase in the muscle fiber diameter was found in the HFD group compared to control one. In addition, significant reductions (P<0.01) in satellite cell frequency and number of myonuclei were detected in the HFD group compared to control group. This study showed that long‐term feeding with HFD increases the size of skeletal muscle fibers, which may be attributed to the accumulation of intramyocellular lipids. In addition, it reveals that HFD decreases the numbers of satellite cells and myonuclei within the murine skeletal muscle fibers. Support or Funding Information Funds for this study were provided by a seeding grant to MZA from the College of Medicine and Health Sciences at United Arab Emirates University.
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