Effect of adrenalectomy and glycemic status on caloric efficiency and adiposity in the congenic LA/Ntul//-cp (corpulent) rat

Abstract

Obesity develops in the obese phenotype of the congenic LA/Ntul//-cp (corpulent) rat strain by 6 weeks of age.1 To gain insight into the contributors to the expression of obesity in the obese phenotype of this strain, groups [n=12-20 rats/phenotype] of congenic male lean and obese LA/Ntul//-cp (corpulent) rats were fed an ad libitum standardized Purina chow diet (CHOW) from 6 to 12 weeks or age, and subgroups (n=6 rats / subgroup) were overfed with a highly palatable cafeteria diet (CAFÉ) from 9 to 12 weeks of age (WOA). A subgroup of obese rats (n=6) were subjected to bilateral adrenalectomy (ADX) at 6 WOA and followed the same dietary regimen and treatment schedule. BW of lean and obese animals were similar at 6 WOA and increased by 88% in lean phenotype and 281% in obese phenotype during the 6 weeks study, while in ADX obese rats, BW were similar at 6 and 9 WOA but BW increased to 2.5-fold above starting weights and 1.8-fold above 9-week weights between 9 and 12 WOA. The CAFE supplement was without significant effect on final body weights in the lean phenotypes, but was associated with significantly greater body weights at ages 9 and 12 WOA in the obese phenotype (p=<0.05) and in the obese-ADX at 12 WOA. CE (kcal/gram gain of BW per day) remained relatively constant in lean and obese-ADX rats throughout the study, but CE was more efficient in the obese phenotype at all ages studied and was more efficient with the CAFE supplement feeding regimen. Fasting I:G ratios at 12 weeks of age were 4.2-fold greater in obese than lean and were partially normalized in obese-ADX to 1.7-fold increase at 12 WOA. Relative adiposity of obese rats was 3.8-fold greater in obese than lean phenotype, with the greatest increase in the SQ depot. Resting VO2 (RMR) was lower in obese than lean rats at each age studied and was increased by ADX. Thermogenic interscapular brown adipose tissue (IBAT) mass was greater in obese and obese-ADX than lean rats. The results of this study indicate that CE is associated with the predisposition for the expression and development of adiposity in the obese phenotype of this strain and is associated with an increased I:G ratio and IBAT mass that is consistent with insulin resistance and an impaired capacity for energy expenditure and became normalized on the Chow but not the CAFE diet following ADX. These observations implicate likely multiple metabolic factors that contribute to a greater efficiency of energy storage, utilization and or energy conservation in the obese than in the lean phenotype of this strain and which is partially corrected in the obese phenotype by ADX. The metabolic impact of added caloric intake was associated with an additive impact on the CE of weight gain and adiposity in the obese phenotype of this congenic rodent strain and was partially corrected via ADX