Skeletal Muscle Transcriptomic Responses to a High-Fat, High-Sugar Diet Across Sex and Maturation in Mice

Background/Objective: Pediatric obesity represents a paramount problem for global health that affects children’s actual quality of life, dramatically compromising their future health. Obesity has been demonstrated to alter skeletal muscle, a highly plastic tissue with dimorphic characteristics, which changes during development, homeostasis, adaptive responses, and diseases. Since it is responsible for 80% of insulin-stimulated glucose uptake, its alteration establishes a vicious circle profoundly impacting overall metabolism. Although obesogenic diets are known to distinctly affect adult male and female muscles, scarce information is available on growing individuals. Therefore, we performed an exploratory analysis on the early effects of an obesogenic diet in murine muscles during maturation. Methods: We analyzed the transcriptome of tibialis anterior from C57BL/6J male and female mice, fed on a high-fat, high-sugar diet (HFHS) for 4 and 20 weeks starting at 3 weeks of age. Results: Experimental data revealed different HFHS-associated transcriptional patterns in female and male mice, within a background of sex-associated transcriptional differences across muscle maturation. Conclusions: These preliminary observations lay the groundwork for further investigation of the mechanisms underlying the differences in diet-associated transcriptional patterns between female and male skeletal muscle, with the ultimate goal of addressing obesity and its comorbidities.