Decreased brown fat markedly enhances susceptibility to diet-induced obesity, diabetes, and hyperlipidemia
Decreased brown fat markedly enhances susceptibility to diet-induced obesity, diabetes, and hyperlipidemia
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DOI：
10.1210/en.137.1.21
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发表时间：
1996-01-01
期刊：
影响因子：
4.8
通讯作者：
Lowell, BB
中科院分区：
文献类型：
--
作者：
Hamann, A;Flier, JS;Lowell, BB
先前的研究表明，啮齿动物对饮食引起的肥胖有相对的抵抗力，这种抵抗力可能部分是由棕色脂肪组织（BAT）中饮食引起的产热能力介导的。为了验证这一假设，我们给毒素介导BAT消融的UCP-DTA转基因小鼠及其对照幼崽喂食“西方饮食”[脂肪含量21% (wt/wt)]或正常小鼠食物[脂肪含量6.5% (wt/wt)]。断奶（19日龄）开始饲粮。在12周龄时，接受西方饮食的转基因小鼠明显肥胖。接受西方饮食的转基因小鼠的体重和总脂含量的增加明显大于西方饮食（对照小鼠）和BAT的减少（裸鼠）的加性个体效应，表明BAT的减少与饮食之间存在协同相互作用。西方饮食和BAT消融对胰岛素抵抗、高血糖和高脂血症等病态代谢并发症也有协同作用。与其他实验组相比，这些代谢变化伴随着接受西方饮食的UCP-DTA转基因小鼠白色脂肪组织中肿瘤坏死因子- α的表达增加，GLUT4和β(3)-肾上腺素能受体信使RNA的表达减少。如前所述，棕色脂肪减少的转基因小鼠是嗜食的。值得注意的是，与对照组相比，转基因动物的贪食程度是相似的，无论这些动物是喂食食物还是西方饮食。因此，西方饮食对转基因小鼠肥胖的协同效应不是通过进一步刺激食物摄入来介导的。总的来说，本研究证明了BAT的减少与西方饮食之间存在协同作用，导致显著的肥胖及其伴随的疾病，如胰岛素抵抗和高脂血症，并进一步支持了BAT的重要功能是防止饮食性肥胖、糖尿病和胰岛素抵抗的观点。
Previous studies have indicated that rodents are relatively resistant to diet-induced obesity and that this resistance may be mediated in part by the capacity for diet-induced thermogenesis in brown adipose tissue (BAT). To test this hypothesis, we fed UCP-DTA transgenic mice with toxigene-mediated ablation of BAT and their control littermates a ''Western diet'' [21% (wt/wt) fat] or normal mouse chow [6.5% (wt/wt) fat]. The diets were begun at weaning (19 days old). At the age of 12 weeks, transgenic mice receiving the Western diet were markedly obese. The increased body weight and total body lipid content were significantly greater in transgenic mice receiving the Western diet than were the additive individual effects of Western diet (in control mice) and decreased BAT (in chow-fed mice), suggesting a synergistic interaction between diminished BAT and diet. A synergistic effect of Western diet and BAT ablation was also observed for morbid metabolic complications, such as insulin resistance, hyperglycemia, and hyperlipidemia. These metabolic changes were accompanied by increased expression of tumor necrosis factor-alpha and decreased expression of GLUT4 and beta(3)-adrenergic receptor messenger RNA levels in white adipose tissue of UCP-DTA transgenic mice receiving the Western diet compared to those in the other experimental groups. As previously described, transgenic mice with diminished brown fat are hyperphagic. Of note, the degree of hyperphagia in transgenics compared to controls was similar whether the animals were fed chow or a Western diet. Thus, the synergistic effect of Western diet on obesity in transgenic mice was not mediated by a further stimulation of food intake. Overall, this study demonstrates the existence of a synergistic intel action between decreased BAT and Western diet to cause marked obesity and its accompanying disorders, such as insulin resistance and hyperlipidemia, and gives further support for the view that an important function of BAT is protection from diet-induced obesity, diabetes, and insulin resistance.