Short-Term Adaptations in Skeletal Muscle Mitochondrial Oxidative Capacity and Metabolic Pathways to Breaking up Sedentary Behaviors in Overweight or Obese Adults.

Nathan P De Jong,Ken Jones,Paul S Maclean,Audrey Bergouignan,Julie Houck,Jane E B Reusch,Zhaoxing Pan,Daniel H Bessesen,Rachel R Sharp,Matthew R Jackman,Michael C Rudolph

doi:10.3390/nu14030454

Abstract

Breaking up sedentary behavior with short-frequent bouts of physical activity (PA) differentially influences metabolic health compared with the performance of a single-continuous bout of PA matched for total active time. However, the underlying mechanisms are unknown. We compared skeletal muscle mitochondrial respiration (high-resolution respirometry) and molecular adaptations (RNA sequencing) following 4-day exposure to breaks vs. energy-matched single-continuous PA bout in inactive adults with overweight/obesity. Participants (9M/10F, 32.2 ± 6.4 years, 30.3 ± 3.0 kg/m2) completed three 4-day interventions of a randomized cross-over study: SED, sedentary control; MICRO, 5 min brisk walking each hour for 9 h; ONE: 45 min/d continuous brisk walking bout. Fasted muscle biopsies were collected on day 5. Mitochondrial coupling in the presence of lipid-associated substrates was higher after ONE (4.8 ± 2.5) compared to MICRO (3.1 ± 1.1, p = 0.02) and SED (2.3 ± 1.0, p = 0.001). Respiratory rates did not differ across groups with carbohydrate-associated substrates. In pathways associated with muscle contraction transcription signaling, ONE and MICRO similarly enhanced Oxidative Phosphorylation and Sirtuin Signaling expression (p < 0.0001, for both). However, ONE (p < 0.001, for all), but not MICRO, had greater pathway enrichment, including Ca++, mTOR, AMPK, and HIF1α signaling, than SED. Although breaking up sedentary behavior triggered skeletal muscle molecular adaptations favoring oxidative capacity, it did not improve mitochondrial function over the short term.

Highlights

Prolonged sedentary behaviors (SB), defined as “any waking behavior characterized by an energy expenditure ≤1.5 metabolic equivalents while in a sitting, reclining, or lying posture” [1], are detrimental for health
A subsample of participants had fasting muscle biopsies harvested for measurement of mitochondrial oxygen consumption in permeabilized muscle fibers (N = 19, 9 males and 10 females) and a subsample for RNA sequencing and pathway analysis (N = 8, 4 males and 4 females)
Breaking up SB with short-frequent bouts of physical activity (PA) spread throughout the day over the short-term (4 days) is a sufficient stimulus to promote changes in the regulation of skeletal muscle gene expression in pathways associated with substrate oxidation

Summary

Introduction

Prolonged sedentary behaviors (SB), defined as “any waking behavior characterized by an energy expenditure ≤1.5 metabolic equivalents while in a sitting, reclining, or lying posture” [1], are detrimental for health. It has been negatively associated with common risk factors for cardiometabolic disease, such as waist circumference, body mass index (BMI, kg/m2 ), 2 h postprandial glycemia, fasting plasma glucose, triglycerides (TG), and. To investigate the independent effects of the active breaks, the metabolic response of short-frequent PA bouts performed throughout the day have been compared to a timematched single-continuous bout Those studies have highlighted that for same total active time and/or energy expenditure, differential metabolic effects are elicited by these different

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Conclusion