Impact of 4 weeks of western diet and aerobic exercise training on whole‐body phenotype and skeletal muscle mitochondrial respiration in male and female mice

Abstract

High dietary fat intake induces significant whole-body and skeletal muscle adaptations in mice, including increased capacity for fat oxidation and mitochondrial biogenesis. The impact of a diet that is high in fat and simple sugars (i.e., western diet [WD]), particularly on regulation of skeletal muscle mitochondrial function, is less understood. The purpose of the current study was to determine physiologic adaptations in mitochondrial respiratory capacity in skeletal muscle during short-term consumption of WD, including if adaptive responses to WD-feeding

Differential effects of Western diet and traumatic muscle injury on skeletal muscle metabolic regulation in male and female mice

“…In the current study, there were several differential outcomes in males and females. Females, for example, demonstrated some compensatory WD adaptations (e.g., absolute muscle mass), which is consistent with previous studies reporting female protection against high‐fat diet‐derived obesity 30,35 . To date, numerous studies have revealed that females have greater mitochondrial content and mitochondrial biogenesis‐related gene responses compared to males; notably, quantifying sex differences was outside the statistical model for our study 36,37 .…”

High‐fat diet increases electron transfer flavoprotein synthesis and lipid respiration in skeletal muscle during exercise training in female mice

“…but not female mice (Ehrlicher et al, 2020;McGowan et al, 2022). The females in our current training protocol improved performance during graded exercise tests, yet it is possible that lower absolute work in females or lack of robust training stimulus may contribute to why there were no major changes in glucose homeostasis nor body composition.…”

“…Our purpose was to investigate ETF abundance and turnover in female mice as a mechanism contributing to changes in mitochondrial fat oxidation to HFD and exercise. HFD increases lipid respiration in males (Ehrlicher et al., 2020), which often have lower respiration than females (Cardinale et al., 2018; McGowan et al., 2022; Miotto et al., 2018; Montero et al., 2018). We studied female mice to determine if lipid respiration can be further stimulated amidst a background of higher intrinsic lipid respiration.…”

“…A study comparing the effects of 20 weeks of HFD in male and female C57BL/6J mice showed that male mice were more susceptible to weight gain within 2 weeks of starting HFD, which was accompanied by reduced locomotor activity (Casimiro et al., 2021). Reduced activity could lead to exercise training being more of a stimulus for male compared to female mice, which may contribute to robust exercise responses in male but not female mice (Ehrlicher et al., 2020; McGowan et al., 2022). The females in our current training protocol improved performance during graded exercise tests, yet it is possible that lower absolute work in females or lack of robust training stimulus may contribute to why there were no major changes in glucose homeostasis nor body composition.…”

“…Glucose tolerance tests (GTT) and insulin tolerance tests (ITT) were performed in unrestrained mice at baseline and repeated at 4 weeks and 12 weeks. Mice were fasted and placed in individual cages with free access to water for 6 h prior to the GTT and 4 h prior to the ITT as described (Ehrlicher et al., 2020; McGowan et al., 2022; Newsom et al., 2017). Body weight was recorded after the fasting period to calculate injection volumes.…”