Sex Differences in the Skeletal Muscle Response to a High Fat, High Sucrose Diet in Rats

Area of Science:

• Endocrinology
• Metabolic Disease
• Skeletal Muscle Physiology

Background:

• Men are diagnosed with type 2 diabetes at lower body mass indexes than women, suggesting sex-specific biological factors.
• Skeletal muscle plays a crucial role in type 2 diabetes, with females exhibiting lower oxidative capacity than males.
• The underlying mechanisms of sex disparities in skeletal muscle's response to metabolic challenges remain poorly understood.

Purpose of the Study:

• To investigate sex-specific adaptations in skeletal muscle mitochondrial respiration in response to a chronic high-fat, high-sugar (HFHS) diet.
• To identify sex-specific differences in mitochondrial characteristics, gene expression, and protein profiles in Wistar rats fed an HFHS diet.

Main Methods:

• Wistar rats (male and female) were fed a standard chow or HFHS diet for 14 weeks.
• Evaluated skeletal muscle mitochondrial respiration, synthesis, dynamics, and quality.
• Performed transcriptomic analyses to assess gene expression patterns related to nutrient handling and signaling pathways.

Main Results:

• HFHS diet increased fat mass in both sexes.
• Males and HFHS-fed rats exhibited higher blood glucose and insulin resistance.
• HFHS-fed males showed significantly higher mitochondrial respiration compared to females, indicating a sex/diet interaction.

Conclusions:

• Sex-specific differences in nutrient handling and signaling pathways (PI3K/AKT, PPARα/RXRα, triacylglycerol degradation) were identified.
• These findings offer insights into the clinical sex differences in type 2 diabetes development and insulin resistance progression.
• Skeletal muscle mitochondrial respiration differences between sexes may contribute to the varying susceptibility to type 2 diabetes.