The effect of phenotype on development of brown and white adipose tissue cellularity and nonshivering thermogenesis in the wistar fatty rat

Abstract

Brown adipose tissue (BAT) has 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 reported to exhibit NIDDM and an impaired thermogenic response to parameters of diet and environment in the obese phenotype. Groups of lean and obese male WFR rats were maintained 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 from 22 to 30 weeks of age. Measures of body weight were monitored and measures of resting, and norepinephrine stimulated VO2 determined. 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. The studies included measures of adipocyte lipid content and adipocyte number of WAT depots including the dorsal (DOR), epididymal (EPI) and visceral retroperitoneal (VRP) depots. Final Body weights, net weight gain and relative adiposity of obese were significantly greater than their lean littermates 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 results of this study indicate 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. Moreover, the increased BAT mass and cellularity in the Obese+NIDDM was not by itself a reliable predictor of the thermic responses to diet and environment.

Insulin resistance, the unbrowning of brown adipose tissue and beige adipose tissue development in obese and obese-diabetic rats: Is there a link?

“…The recent reports of beige adipose tissue, also identified as beige, bright, or pink adipose tissue suggest beige adipose tissue may have a role in energy balance vs. energy storage Table 1 below, the BAT depots are well developed and appear to have undergone significant increases in BAT depot mass and cellularity, consistent with early hyperplasia, hypertrophy and lipid accretion in the BAT depots, particularly the Interscapular depot where most studies have focused. 8,[15][16][17][18][19][20] The histologic features of white and brown adipocytes are markedly different: white adipocytes are readily identified in histologic specimens by their single large lipid droplet, which typically occupies up to 90% or more of the morphology of the adipocyte structure. The single large lipid droplet is typically surrounded with a narrow rim of cytoplasmic material, a defined plasma membrane and a peripherally located and often ovoid-shaped nucleus compressed into the cytoplasmic rim.…”

“…26 The epigenetic expression of an obese phenotype may also develop in the absence of NIDDM in some obesity-prone strains. 14,15,19 The increases in BAT mass in obese rats is disproportionate however to the magnitude of thermogenesis typically observed, in that resting and norepinephrine stimulated VO2 remain depressed among the obese phenotype in spite of the increases in BAT mass and cellularity. [14][15][16][17][18][19] Insulin resistance occurs in the obese phenotype of several obese rodent strains, including the Obese, nondiabetic Zucker fatty (-fa) rat and the LA/Ntul//-cp (Corpulent ) rat and the NIDDM strains including the T2DM Wistar Fatty Rat, and the obese T2DM SHR/Ntul//-cp (Corpulent) rat, and the WKY/N-cp rats with the greatest magnitude of IR among the obese+diabetes prone strains.…”

“…14,15,19 The increases in BAT mass in obese rats is disproportionate however to the magnitude of thermogenesis typically observed, in that resting and norepinephrine stimulated VO2 remain depressed among the obese phenotype in spite of the increases in BAT mass and cellularity. [14][15][16][17][18][19] Insulin resistance occurs in the obese phenotype of several obese rodent strains, including the Obese, nondiabetic Zucker fatty (-fa) rat and the LA/Ntul//-cp (Corpulent ) rat and the NIDDM strains including the T2DM Wistar Fatty Rat, and the obese T2DM SHR/Ntul//-cp (Corpulent) rat, and the WKY/N-cp rats with the greatest magnitude of IR among the obese+diabetes prone strains. [14][15][16][17][18][19] Hyperplasia and hypertrophy of BAT occurs in both non-T2DN and in obese-T2DM /NIDDM strains and it becomes visibly evident by inspection during early postweaning and later growth, and by early adulthood hypertrophy of the BAT tissues became readily apparent due to the less intense brown coloration of the tissue noted during gross dissections.…”

“…[14][15][16][17][18][19] Insulin resistance occurs in the obese phenotype of several obese rodent strains, including the Obese, nondiabetic Zucker fatty (-fa) rat and the LA/Ntul//-cp (Corpulent ) rat and the NIDDM strains including the T2DM Wistar Fatty Rat, and the obese T2DM SHR/Ntul//-cp (Corpulent) rat, and the WKY/N-cp rats with the greatest magnitude of IR among the obese+diabetes prone strains. [14][15][16][17][18][19] Hyperplasia and hypertrophy of BAT occurs in both non-T2DN and in obese-T2DM /NIDDM strains and it becomes visibly evident by inspection during early postweaning and later growth, and by early adulthood hypertrophy of the BAT tissues became readily apparent due to the less intense brown coloration of the tissue noted during gross dissections. In such animals, it has been found in association with a less intense brown coloration as the adipocytes as they accumulate additional lipid reserves when insulin resistance occurs.…”

“…10,11 Circulating plasma concentrations of triiodothyronine (T3) also contributes to an optimal thermogenic response in rats, and along with RMR are also commonly decreased among the obese phenotype of epigenetically obesity-prone strains. [14][15][16][17][18][19] Café' feeding regimes in both lean and obese rats results in increases in BAT mass, plasma T3 concentrations, Vanilmandelic acid (VMA) excretion, RMR, and norepinephrine stimulated VO2, while pharmacologic sympathomimetic blockade via α-methylparatyrosine results in decreases in VMA and the magnitude of the sympathetic component of the thermogenic responses. [26][27][28]…”