Cellular and Molecular Variations in Male and Female Murine Skeletal Muscle after Long-Term Feeding with a High-Fat Diet.

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.

Association of VEGFA variants with altered VEGF secretion and type 2 diabetes: A case-control study.

BACKGROUND: Vascular endothelial growth factor (VEGF) contributes to type 2 diabetes (T2DM) pathogenesis, and genetic variations in VEGFA gene were suggested to influence VEGF secretion and T2DM pathogenesis. AIM: To evaluate the association of specific VEGFA variants with altered VEGF levels, and with T2DM among Tunisians. SUBJECTS AND METHODS: A retrospective case-control study, performed on 815 T2DM patients, and 805 healthy controls. VEGF levels were measured by ELISA, genotyping of VEGFA variants was done by allelic exclusion method (real-time PCR). RESULTS: MAF of rs1570360, rs2010963, rs25648, rs833068, rs3025036, and rs3025039 were significantly different between T2DM cases and controls. Increased T2DM risk was associated with rs699947, rs1570360, and rs3025020, while reduced T2DM risk was seen with rs1547651, rs2010963, rs25648, rs3025036, and rs3025039 genotypes, thus assigning T2DM susceptibility and protection, respectively. Reduced VEGF levels were associated with rs833061, rs2010963, and rs3025039 heterozygosity and rs3025036 major allele homozygosity in T2DM cases, while increased VEGF levels were seen in rs833070 homozygous major allele genotype. Both rs699947 and rs1570360 positively, while rs2010963 and rs3025036 negatively correlated with fasting glucose. In addition, rs699947 positively correlated with LDL-cholesterol, and rs3025039 positively correlated with diabetes duration, but negatively with HbA1c and serum triglycerides. Haploview analysis identified Block 1 containing 8 loci, and Block 2 with the remaining 3 loci. Haplotypes ACTGCCGG and AACGGCGA (Block 1) were negatively associated with T2DM, while haplotype CCC was positively and haplotype CGC (Block 2) were negatively associated with T2DM. CONCLUSION: This study confirms the contribution of altered VEGF secretion, resulting from genetic variation in VEGFA gene into T2DM pathogenesis, hence supporting role for VEGFA as T2DM candidate locus.