Thermogenesis, aging and obesity in the LA Ntul/-cp (corpulent) rat

Abstract

Obesity and mild to moderate impaired carbohydrate tolerance develops in the obese phenotype of the LA/Ntul//-cp (corpulent) rat strain by 6 weeks of age. Groups (n=12-20 rats/phenotype] of female congenic lean and obese LA/Ntul//-cp (corpulent) rats were fed ad libitum standardized Purina #5012 diet ad house water for 4, 14, or 24 months of age. Measures of Body weight (BW) and of resting oxygen consumption (RMR; VO2) at thermal neutrality and for up to 45 minutes of (4°C) spontaneous cold exposure, and norepinephrine-stimulated thermogenesis (100 ug. s.c.) were determined at each age. Body weights of lean rats increased only gradually during the study (p=n.s.), but weights of obese phenotype were ~2-fold greater at 4 months (p=<0.05), 14 months (p-<0.01), and ~3.5 to 4-fold greater at 24 months of age (p=<0.01). Resting metabolic rates in the lean phenotype trended to decrease modestly by 24 months (p=<0.05) and were greater than resting metabolic rates in the obese phenotype at all ages studied (p=<0.05). Cold exposure at 4°C resulted in a dramatic ~5-fold increase in the oxygen consumption after 5 minutes in 4-month-old rats, which subsided to ~2x resting metabolic rate within 15 minutes and remained constant thereafter in the lean phenotype. In 14-months old lean rats the increase in oxygen consumption at 5 minutes averaged ~4-fold increase over resting levels and returned to ~2x resting levels from 15 to 45 minutes 4°C exposure. In 24-month-old lean rats however, the cold induced increases in metabolism were markedly diminished to only ~3x resting metabolic rates at 5 minutes cold exposure but remained similar to the other lean age groups thereafter. In the obese phenotype, the peak responses at 5 minutes were lower than those of lean rats at 5 minutes in 4- and 14-month-old rats and were significantly impaired in 24-month-old rats at all times measured. Norepinephrine resulted in a >1.5-fold increase in oxygen consumption in the lean phenotype at all ages studied, while in obese rats norepinephrine resulted in a~1.4-fold increase in oxygen consumption at 4 months of age with non-significant ~1.1 to 1.2-fold increases at the two older ages. In both phenotypes, the resting and the norepinephrine-stimulated oxygen consumption responses tended to decrease with increasing age. The results of this study demonstrate that the body weights of the obese phenotype are significantly greater than their lean littermates throughout the age spectrum studied, and that both resting metabolic rates, 4°C cold, and norepinephrine-stimulated thermogenesis are decreased in the obese compared to the lean phenotype and become further decreased with advancing age