肾上腺切除术和血糖状态对先天性LA/Ntul/ -cp(肥胖)大鼠热效率和肥胖的影响

O. Tulp, A. Awan, George P Einstein
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摘要

基因LA/Ntul//-cp(肥胖)大鼠在6周龄时出现肥胖表型为了深入了解该品系肥胖表型中肥胖表达的因素,在6 - 12周龄(WOA)期间,将遗传雄性瘦肉和肥胖LA/Ntul//-cp(肥胖)大鼠[n=12-20只大鼠/表型]随意喂食标准化普瑞纳饲料(chow),亚组(n=6只大鼠/亚组)在9 - 12周龄(WOA)期间过量喂食高度美味的自助饮食(CAFÉ)。肥胖大鼠亚组(n=6)在6 WOA时接受双侧肾上腺切除术(ADX),并遵循相同的饮食方案和治疗计划。瘦肉和肥胖动物的体重在6 WOA时相似,在6周的研究期间,瘦肉表型和肥胖表型的体重分别增加了88%和281%,而ADX肥胖大鼠的体重在6和9 WOA时相似,但在9和12 WOA期间,体重增加到初始体重的2.5倍和9周体重的1.8倍。在瘦表型中,补充CAFE对最终体重没有显著影响,但在肥胖表型中,9岁和12 WOA时体重显著增加(p=<0.05),在肥胖- adx中,12 WOA时体重显著增加。在整个研究过程中,瘦肉大鼠和肥胖- adx大鼠的CE (kcal/g gain of BW / day)保持相对恒定,但CE在所有年龄的肥胖表型中都更有效,并且在CAFE补充喂养方案中更有效。12周龄时,肥胖的空腹I:G比值比瘦的高4.2倍,肥胖的空腹I:G比值在12 WOA时部分正常化至1.7倍。肥胖大鼠的相对肥胖表型比瘦型大3.8倍,SQ库增加最多。在研究的每个年龄,肥胖大鼠的静息VO2 (RMR)低于瘦大鼠,ADX使其升高。肥胖大鼠和肥胖- adx大鼠的产热性肩胛间棕色脂肪组织(IBAT)质量大于瘦大鼠。本研究的结果表明,CE与该品系肥胖表型中肥胖的表达和发展倾向有关,并与I:G比和IBAT质量的增加有关,这与胰岛素抵抗和能量消耗能力受损一致,并在ADX后在Chow饮食中恢复正常,而在CAFE饮食中则没有。这些观察结果表明,可能存在多种代谢因素,这些因素导致肥胖菌株的能量储存、利用和/或能量节约效率高于瘦型菌株,而ADX在肥胖表型中部分纠正了这一点。增加热量摄入的代谢影响与肥胖表型中体重增加和肥胖的累加性影响相关,并通过ADX部分纠正
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Effect of adrenalectomy and glycemic status on caloric efficiency and adiposity in the congenic LA/Ntul//-cp (corpulent) rat
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
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