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.

Fig. 1.

Complete oxidation of palmitate to CO₂ in whole red gastrocnemius homogenate (A) and isolated mitochondria from red gastrocnemius (B). WL5, wheel lock for 5 h group; WL173, wheel lock for 173 h group; SED, sedentary. In A, there is a main effect P value of 0.059. Values are means ± SE; n = 6–8/group. Values with different letters are significantly different (P < 0.05).

Fig. 2.

Complete oxidation of palmitate to CO₂ in whole liver homogenate (A) and isolated mitochondria from liver (B). Values are means ± SE; n = 6–8/group. Values with different letters are significantly different (P < 0.05).

Fig. 3.

Complete oxidation of palmitate to CO₂ in isolated adipocytes from the epididymal fat pad normalized to nanograms of DNA per 30 μl of packed adipocytes (A) or to volume (μl) of packed adipocytes (B). Values are means ± SE; n = 6–8/group. Values with different letters are significantly different (P < 0.05).

Fig. 4.

Carnitine palmitoyltransferase-1 (CPT-1) activities in isolated mitochondria from red gastrocnemius muscle (A) and liver (B). CPT-1 activity was measured in the absence (solid bars) or presence of an inhibitory amount of malonyl-CoA (10 μM, shaded bars), and expressed as the difference between the malonyl-CoA doses (delta, open bars). Data are normalized to 1 in WL5 group and then expressed relative to WL5. Values are means ± SE; n = 6–8/group. Values with different letters are significantly different (P < 0.05).

Fig. 5.

Peroxisome proliferator-activated receptor coactivator-1α (PGC-1α) mRNA in red gastrocnemius (A), liver (B), and epididymal adipose tissue (C). Data are normalized to 18S expression and expressed in fold difference. Values are means ± SE; n = 6–8/group. Values with different letters are significantly different (P < 0.05).