Decreased Capacity for Thermogenesis During Aging in Lean and Obese LA/Ntul//‐ cp (corpulent) Rats

Obesity 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 congenic female lean and obese LA/Ntul//-cp (corpulent) rats were fed ad libitum standardized Purina #5012 diet for 4, 14, or 24 months of age. Measures of Body weight (BW) and of resting metabolic rate (RMR) at thermal neutrality, and for up to 45 minutes of 4°C spontaneous cold exposure, and norepinephrine-stimulated (NE) thermogenesis (100 µg sc) were determined at each age. BW of lean rats increased only gradually during the study (p=N.S.), but BW of obese phenotype were 2-fold greater at 4 months (p=0.05) and increased progressively to 4-fold greater than lean littermates by 24 months of age (p=<0.01). RMR in the lean phenotype decreased gradually at each age (p=<0.05) and was greater in the lean than the obese phenotype at all ages studied (p=<0.05). Cold exposure resulted in a dramatic 5-fold increase in the VO2 after 5 minutes in 4-month-old rats, which increase in thermogenesis was less dramatic at each successive age. In 24-month-old lean rats however, the cold induced increases in RMR were markedly diminished to only ~3x RMR 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 significantly lower than those of lean rats at 5 minutes in 4- and 14-month-old rats and were also markedly impaired in 24-month-old obese rats. NE resulted in a 1.5-fold increase in VO2 in the lean phenotype at all ages studied, while in obese rats NE resulted in a ~1.4-fold increase in VO2 at 4 months with non-significant 1.2-fold increases at the two older ages. In both phenotypes, the RMR and the NE-stimulated VO2 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 from 6 weeks of age, and that both resting RMR, cold, and NE-stimulated thermogenesis are decreased in the obese compared to the lean phenotype, become further decreased with advancing age, and may be a contributing factor in the efficiency of energy conservation and expenditure in the obese phenotype of this animal strain.