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

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.

Physiology of sedentary behavior

“…In contrast, there were no differences in pAS160 Thr642 /AS160 ratio and GLUT4 protein expression in the skeletal muscle of postmenopausal females with rheumatoid arthritis following light-intensity walking interruptions to sitting (~25% heart rate reserve, 3-minute bouts every 30 minutes, total: 42 minutes) compared to 8 hours of prolonged sitting (213). Finally, although acute exposure to moderate-intensity active interruptions in adults with overweight/obesity was associated with increased gene expression of complex V of the electron transport chain indicating greater capacity for ATP production (226), four days of moderatewalking interruptions to sitting (perceived effort: 12-13 "somewhat hard", 5-minute bouts every hour, total: 45 minutes/day) did not elicit changes in mitochondrial respiration in presence of carbohydrates (227); of note this later measurement was performed in fasting state and >12 hours after the last active interruption. Notably, pathways associated with muscle contraction transcription signaling, namely oxidative phosphorylation and sirtuin signaling expression, were enhanced in the skeletal muscle of these same participants when compared to a highly sedentary condition, as indicated by pathway enrichment analysis with RNA sequencing data (227).…”

Breaking up sedentary time to improve glucose control in a population at risk for developing type 2 diabetes (BURST2D study): a randomized controlled trial

“…18 In adults with overweight/obesity favorable changes in skeletal muscle gene and protein expression were observed acute (5-h) and short-term (3-4 days) exposure to breaking up SB with short bouts of PA that likely contribute to improved cellular glucose uptake, insulin signaling cascade and oxidative capacity. 19,20 These changes include some which align with, and others which are distinct from, the known effects of continuous acute PA. [19][20][21] The 2016 position statement on PA and diabetes from the American Diabetes Association, the 2018 U.S. PA guidelines and the American college of sports medicine PA recommendations for T2D include recommendations to reduce and interrupt prolonged sitting. [22][23][24] Most studies on the effects of reducing and interrupting prolonged SB on glycemic control have mostly been acute (<1-4 d) and conducted in controlled laboratory settings or derived from population-level evidence.…”

Oral Ionic Liquid for Transdermal Delivery and Obesity Treatment

“…It is estimated that the global economic burden used to control obesity, and its complications is two trillion U.S. dollars each year, accounting for 2.8% of global GDP . Various factors (diet, genetics, stress, sedentary, and social and environmental factors) are associated with the development of obesity. − …”