Epigenetic Expression of Brown and White Tissue Development and Thermogenesis in the Wistar Fatty Rat

Abstract

The primary physiologic function of brown adipose tissue (BAT) is now known to contribute to processes of energy expenditure in the form of heat in response to alterations in diet and environment. BAT depots have been noted in cadaveric specimens by anatomists for hundreds of years and is now known to be a primary peripheral tissue in the expression of non-shivering thermogenesis in response to perturbations in diet and environment in homeothermic species including man and animals. The Wistar Fatty Rat (WFR) is an animal model of obesity, insulin resistance (IR) and NIDDM and expresses the (-fa) obesity trait in an NIH/Wistar background. This stain has been linked to NIDDM and an impaired thermogenic response to diet and environment parameters in the obese phenotype. From 22 to 30 weeks of age, groups of lean and obese male WFR rats were kept in hanging wire-bottomed steel cages and fed a nutritionally complete diet containing 54% CHO as equal parts cornstarch (ST) and sucrose (SUC) (50:60 w/w) plus vitamins, minerals, fiber, and essential micronutrients. Body weight was measured, and resting and norepinephrine-stimulated VO2 were calculated. Animals were sacrificed by decapitation and the Interscapular BAT depot (IBAT) and primary white adipose tissue (WAT) depots excised in their entirety for measures of adiposity including adipocyte size and number per IBAT and WAT depots. Obese people had significantly higher final body weights, net weight gain, and relative adiposity than lean people throughout the study, with the greatest increase in WAT cell lipid content and adipocyte number in the VRP depot. IBAT cell number, cell lipid content of IBAT tissues and IBAT:BW ratio of obese >> lean littermates. Fasting glucose was similar in both phenotypes, but fasting insulin and the Insulin: Glucose (I: G) ratios were markedly elevated in obese+NIDDM animals. Resting VO2 and the thermic response to NE of lean >> Obese+NIDDM. A robust NE response in plasma glucose concentrations occurred in both phenotypes following NE with the greatest increase in the obese+NIDDM phenotype. The findings of this study suggest that, while the development of IBAT and WAT mass and cellularity became exaggerated via hyperplasia and hypertrophy in the obese-NIDDM animals, the superimposition of early hyperphagia and the NIDDM stigmata which likely includes the development of significant IR is a contributing factor. The elevations in I: G and IR of the Obese+NIDDM phenotype may further facilitate adipocyte hyperplasia and hypertrophy in both WAT and BAT depots and may further compromise the capacity of the obese diabetic animals to fully express BAT-mediated contributions to NST. Furthermore, increased BAT mass and cellularity in Obese+NIDDM patients was not a reliable predictor of thermic responses to diet and environment.