Influence of endurance training on the age-related decline in hepatic glyconeogenesis

Hepatic gluconeogenic and glyconeogenic capabilities were investigated in Fischer 344 rat livers (ages 7, 15 and 25 months; n = 66) to determine if endurance training affected age related decrements in these hepatic functions. Animals were trained 1 h/day, 5 days/week for 10 weeks at treadmill speeds of 75% of age-specific maximal capacity. After training, rats were injected (300 mg/kg) with a known gluconeogenic inhibitor, 3-mercaptopicolinic acid (MPA). Two endurance tests were performed to help assess the contribution of gluconeogenesis to exercise performance, an initial test 4 days prior to injection and a final test immediately post-injection. MPA significantly (P < 0.05) reduced running times in all trained groups compared to their control test: 89%, 81%, and 51% in the young, middle-aged, and old, respectively. MPA reduced running times in the untrained animals 19%, 11%, and 8%, respectively. Three days after the last exercise bout, the animals were anesthetized and liver sections were sliced and incubated in [¹⁴C]lactic acid or [¹⁴C]fructose. An age-related decline was found in [¹⁴C]lactate incorporation (middle-aged 166%, old 154%) and in [¹⁴C]fructose incorporation (middle-aged 151%, old 148%) into glycogen. Differences existed in lactate incorporation in trained compared to untrained animals for the young, middle-aged, and old groups: 150.1 ± 11.3 vs. 102.1 ± 10.0; 75.3 ± 6.2 vs. 34.9 ± 6.4; and 69.3 ± 14.9 vs. 47.0 ± 4.7 nmol/g/h, respectively. No differences were found with training in any of the age groups for fructose. Phosphoenolpyruvate carboxykinase (PEPCK) activity and messenger RNA (mRNA) were significantly reduced in the old compared to the young rats (164% and 158%, respectively). No training effects were found for either PEPCK activity or mRNA for any age group. These results suggest that hepatic gluconeogenic and glyconeogenic capabilities declined with age. Training had an effect in attenuating the glyconeogenic decline but had a minimal effect in offsetting the age-related decline in PEPCK.