FIGURE 4.

Carnitine supplementation reverses diet-induced mitochondrial dysregulation. Mitochondria were isolated from mixed gastrocnemius muscles of young (2 month) or old (15 month) male Wistar rats fed either standard chow (SC) or high fat (HF) diet for 12 months, without or with oral carnitine supplementation administered during the final 2 months (HF/Carn). Oxidation of [1-¹⁴C]oleate (100 μm) to ¹⁴CO₂ (a) or ¹⁴C-labeled acid soluble metabolites (ASM; panel b) was measured ± pyruvate (5 mm) as an index of substrate switching. PDH activity (c) and pyruvate oxidation (d) were assessed as the liberation of ¹⁴CO₂ from [1-¹⁴C]pyruvate (5 mm) ± l-carnitine (5 mm) or [2-¹⁴C]pyruvate (5 mm) ± oleate (100 μm), respectively. Data represent means ± S.E. from 5–8 animals per group. A Student's t test was used to evaluate between group differences, and paired t tests were applied to detect within-group responses to pyruvate, carnitine, and oleate. *, p < 0.05 pyruvate-induced inhibition of oleate oxidation; ^$, p < 0.05 difference in substrate switching between SC versus HF diet groups; #, p < 0.05 difference between SC and HF diet groups; ^‡, p < 0.05 effect of l-carnitine on PDH activity; ^, p < 0.05 oleate-induced inhibition of pyruvate oxidation.