Cessation of daily wheel running differentially alters fat oxidation capacity in liver, muscle, and adipose tissue

Abstract

Physical inactivity is associated with the increased risk of developing chronic metabolic diseases. To understand early alterations caused by physical inactivity, we utilize an animal model in which rats are transitioned from daily voluntary wheel running to a sedentary condition. In the hours and days following this transition, adipose tissue mass rapidly increases, due in part to increased lipogenesis. However, whether a concurrent decrease in fatty acid oxidative capacity (FAO) in skeletal muscle, liver, and adipose tissue occurs during this period is unknown. Following 6 wk of access to voluntary running wheels (average distance of approximately 6 km a night), rats were rapidly transitioned to a sedentary state by locking the wheels for 5 h (WL5) or 173 h (WL173). Complete ([(14)C]palmitate oxidation to (14)CO(2)) and incomplete ([(14)C]palmitate oxidation to (14)C-labeled acid soluble metabolites) was determined in isolated mitochondrial and whole homogenate preparations from skeletal muscle and liver and in isolated adipocytes. Strikingly, the elevated complete FAO in the red gastrocnemius at WL5 fell to that of rats that never ran (SED) by WL173. In contrast, hepatic FAO was elevated at WL173 above both WL5 and SED groups, while in isolated adipocytes, FAO remained higher in both running groups (WL5 and WL173) compared with the SED group. The alterations in muscle and liver fat oxidation were associated with changes in carnitine palmitoyl transferase-1 activity and inhibition, but not significant changes in other mitochondrial enzyme activities. In addition, peroxisome proliferator-activated receptor coactivator-1alpha mRNA levels that were higher in both skeletal muscle and liver at WL5 fell to SED levels at WL173. This study is the first to demonstrate that the transition from high to low daily physical activity causes rapid, tissue-specific changes in FAO.

Lipid droplet-associated proteins in high-fat fed mice with the effects of voluntary running and diet change

“…(Brownlow et al 1996.) However, as several recent studies have demonstrated, many pathological metabolic events associated with chronic diseases may be prevented or delayed when physical activity is commenced (Linden et al 2013;Rector et al 2010;Laye 2009;Lakka & Laaksonen 2007). Physical activity is defined by the Centers for Disease Control and Prevention (CDC) as "any bodily movement produced by the contraction of skeletal muscle that increases energy expenditure above a basal level.…”

Metabolic disruptions induced by reduced ambulatory activity in free-living humans

“…Booth and colleagues (27)(28)(29)(30)38) published a series of "wheel lock" studies to determine the mechanisms by which acute inactivity leads to metabolic dysfunction. Rats provided with voluntarily running wheels (VWR) in their cages will voluntarily run during the dark cycle.…”

“…Running volumes can vary from ϳ1 up to 20 km over a 12-h dark cycle period but are typically consistent within experiments. In addition, the mitochondrial adaptations in skeletal muscle after VWR (29,39) are usually very modest and pale in comparison to what is measured in rats forced to run on treadmills (11). Therefore, it could be argued that VWR in rats is analogous to higher daily ambulatory activity in humans, while treadmill running in rats would mimic programmed endurance exercise in humans.…”

“…Bed rest studies, a more extreme model of inactivity, show changes in glucose and fat metabolism that support a repartitioning of energy (4), including a recent report focused on changes in adipose tissue (18). Newer studies in the rodent wheel lock model also show evidence for the repartitioning of energy as there are rapid changes in lipid oxidation and pathways controlling lipid synthesis in muscle, liver, and adipose in the days following a transition to inactivity (29,38). The exact mechanisms are unknown but could be tied back to control of insulin sensitivity at the level of the muscle.…”

Retention of sedentary obese visceral white adipose tissue phenotype with intermittent physical activity despite reduced adiposity

“…There is evidence from rodent (7,18,27) and human (25) studies that cessation of physical activity for 7-10 days is sufficient to increase visceral adiposity. It is not uncommon for humans to transition repetitively from periods of high physical activity to periods of inactivity and vice versa over their lifespan.…”