Effects of a high-fat diet and voluntary wheel running on gluconeogenesis and lipolysis in rats

The purpose of the present study was to determine the effects of diet composition and exercise on glycerol and glucose appearance rate (R(a)) and on nonglycerol gluconeogenesis (Gneo) in vivo. Male Wistar rats were fed a high-starch diet (St, 68% of energy as cornstarch, 12% corn oil) for a 2-wk baseline period and then were randomly assigned to one of four experimental groups: St (n = 7), high-fat (HF; 35% cornstarch, 45% corn oil; n = 8), St with free access to exercise wheels (StEx; n = 7), and HF with free access to exercise wheels (HFEx; n = 7). After 8 wk, glucose R(a) when using [3- ³H]glucose, glycerol R(a) when using [²H₅]glycerol (estimate of whole body lipolysis), and [3-¹³C]alanine incorporation into glucose (estimate of alanine Gneo) were determined. Body weight and fat pad mass were significantly (P < 0.05) decreased in exercise vs. sedentary animals only. The average amount of exercise was not significantly different between StEx (3,212 ± 659 m/day) and HFEx (3,581 ± 765 m/day). The ratio of glucose to alanine enrichment and absolute glycerol R(a) (μmol/min) were higher (P < 0.05) in HF and HFEx compared with St and StEx rats. In separate experiments, the ratio of ³H in C-2 to C-6 of glucose from ³H²O (estimate of Gneo from pyruvate) was also higher (P < 0.05) in HF (n = 5) and HFEx (n = 5), compared with St (n = 5) and StEx (n = 5) rats. Voluntary wheel running did not significantly increase estimated alanine or pyruvate Gneo or absolute glycerol R(a). Voluntary wheel running increased (P < 0.05) glycerol R(a) when normalized to fat pad mass. These data suggest that a high-fat diet can increase in vivo Gneo from precursors that pass through pyruvate. They also suggest that changes in the absolute rate of glycerol R(a) may contribute to the high-fat diet-induced increase in Gneo.