Age-related changes in lipid and carbohydrate metabolism of the genetically obese mouse.

Obese mice (C57BL/6J ob/ob) and their lean controls were studied longitudinally from immediately post-weaning until 62 wk of age, at which time the experiment was terminated. The dynamic nature of the metabolic aberrations of the obese mouse syndrome was clearly demonstrated. Obese mice were hyperinsulinemic at all ages yet the concentration of glucose in plasma was elevated only at 5-20 wk and 63 wk of age, but was similar to that of lean mice at 20-60 wk of age. Triacylglycerols accumulated in the liver of obese mice between 5 and 18 wk of age to a level that was 20-fold greater than that found in the age-matched lean control. A decreased concentration of DNA/g of liver was also found in 5-18 wk-old obese mice, indicative of an enlarged hepatocyte. With the exception of 5-wk-old animals, total DNA per liver was increased in obese mice when compared to the lean control throughout the profile. Following the peak in 18-wk-old mice, the hepatic content of triacylglycerols precipitously fell so that at 45 wk of age its concentration in obese mice was similar to that of the lean control. Plasma free fatty acid levels as well as liver glycogen content were comparable in obese mice and their lean controls throughout the profile. In obese mice older than 45 wk of age, the content of triacylglycerols in plasma was significantly lower than that of the age-matched lean control while an accumulation of liver triacylglycerols was again found in obese mice. Myocardial triacylglycerols were elevated in obese mice when compared to the lean control at all ages. The longitudinal metabolic profile of the obese mouse developed in the present study clearly demonstrates the dynamic nature of the deviations in carbohydrate and lipid metabolism in this animal model of human obesity and insulin resistance.