Exercise-Induced Changes in Caveolin-1, Depletion of Mitochondrial Cholesterol, and the Inhibition of Mitochondrial Swelling in Rat Skeletal Muscle but Not in the Liver

Abstract

The reduction in cholesterol in mitochondria, observed after exercise, is related to the inhibition of mitochondrial swelling. Caveolin-1 (Cav-1) plays an essential role in the regulation of cellular cholesterol metabolism and is required by various signalling pathways. Therefore, the aim of this study was to investigate the effect of prolonged swimming on the mitochondrial Cav-1 concentration; additionally, we identified the results of these changes as they relate to the induction of changes in the mitochondrial swelling and cholesterol in rat skeletal muscle and liver. Male Wistar rats were divided into a sedentary control group and an exercise group. The exercised rats swam for 3 hours and were burdened with an additional 3% of their body weight. After the cessation of exercise, their quadriceps femoris muscles and livers were immediately removed for experimentation. The exercise protocol caused an increase in the Cav-1 concentration in crude muscle mitochondria; this was related to a reduction in the cholesterol level and an inhibition of mitochondrial swelling. There were no changes in rat livers, with the exception of increased markers of oxidative stress in mitochondria. These data indicate the possible role of Cav-1 in the adaptive change in the rat muscle mitochondria following exercise.

Figure 1

Mitochondrial cholesterol levels in controlled and exercised animals. Cholesterol was measured in crude mitochondria isolated from the quadriceps (a) and liver (b). The data are presented as the means ± SE. ^∗ There was a significant difference between the E (exercise) versus C (control) in the Quadriceps mitochondria ^∗ P = 0.001 versus the control rats (n = 6 in each group).

Figure 2

Mitochondrial swelling in controlled and exercised animals. The calcium chloride-induced mitochondrial swelling was spectrophotometrically assessed in the quadriceps (a) and liver (b) crude mitochondria. The data are presented as the means ± SE. ^∗ There was a significant difference between the E (exercise) versus C (control) in the quadriceps mitochondria ^∗ P = 0.002 versus the control rats (n = 6 in each group).

Figure 3

Mitochondrial caveolin-1 levels in controlled and exercised animals. Caveolin-1 level was measured in crude mitochondria isolated from the quadriceps (a) and liver (b). The data are presented as the means ± SE. ^∗ There was a significant difference between the E (exercise) versus C (control) in the quadriceps mitochondria ^∗ P = 0.006 versus the control rats (n = 6 in each group).

Figure 4

Correlation between caveolin-1 and cholesterol levels in quadriceps crude mitochondria. A Pearson product-moment correlation coefficient was computed to assess the relationship between the caveolin-1 and cholesterol level in the crude mitochondria isolated from the quadriceps. There was a large, negative correlation between the two variables, r = −0.67, P = 0.017.

Figure 5

The Cav-1-dependent hypothesis of mitoprotection under exercise conditions. Under physiological conditions: appropriate levels of Cav-1 and cholesterol concentrations are presented in the mitochondria of contractile tissues. Under pathological conditions in crude mitochondria, decreased Cav-1, increased cholesterol concentrations, and mitochondrial swelling are observed. Exercise induces the opposite effects; for example, increased Cav-1 levels and decreased cholesterol levels in mitochondria lead to the inhibition of mitochondria swelling.