Brown and beige adipose tissue: New therapeutic targets for metabolic disorders

Bruno Souza Magro, Daniel Penteado Martins Dias
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Abstract

Brown adipocytes constitute a specialized tissue in heat build-up (i.e., thermogenesis) due to their mitochondrial uncoupling capacity, as they express thermogenic genes, playing a role in the energy metabolism of the whole body in mammals through non-shivering thermogenesis. Beige adipocytes originate in white adipose tissue (WAT) through the tissue browning process and are phenotypically similar to brown adipocytes. Considering that the activity of these cells is essential to reduce the incidence of metabolic diseases, including obesity, type 2 diabetes, and dyslipidemia, the stimulation of the brown fat and the development of beige adipose tissue has become a promising therapeutic target to treat clinical conditions. Due to the low amount of brown adipose tissue (BAT) in human adults, both phenomena (i.e., activation of brown and development of beige adipocytes) are related to better control of body weight, adiposity, insulin resistance, and hyperlipidemia. This review focuses on the comprehensively discussion of the metabolic importance of BAT activation and/or browning of WAT, and approaches that lead to the biogenesis of these thermogenic fats, such as cold exposure, thyroid hormones, physical exercise, diet and pharmacological agents (i.e., β3-adrenergic receptor agonist, glucagon-like peptide 1, mineralocorticoid receptor antagonists, ephedrine). These stimulatory agents have shown promise in activating BAT in humans. Frow our review, concluded that there are still many obstacles to be overcome in the upcoming years to better assess the real impact of BAT activation on metabolic health (i.e., absence of insulin resistance and metabolic syndrome), and elucidate many questions surrounding BAT physiology, so that this organ can indeed be considered an attractive therapeutic target for the prevention and reversal of obesity and metabolic disorders.

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棕色和米色脂肪组织:代谢紊乱的新治疗目标
棕色脂肪细胞因其线粒体解偶联能力而成为热量积累(即产热)的专门组织,因为它们表达产热基因,通过非颤抖性产热在哺乳动物全身的能量代谢中发挥作用。米色脂肪细胞通过组织褐变过程起源于白色脂肪组织(WAT),在表型上与棕色脂肪细胞相似。考虑到这些细胞的活性对降低代谢性疾病(包括肥胖、2 型糖尿病和血脂异常)的发病率至关重要,刺激棕色脂肪和米色脂肪组织的发育已成为治疗临床疾病的一个很有前景的治疗目标。由于人类成年人的棕色脂肪组织(BAT)数量较少,这两种现象(即棕色脂肪细胞的激活和米色脂肪细胞的发育)都与更好地控制体重、脂肪过多、胰岛素抵抗和高脂血症有关。这篇综述重点全面讨论了 BAT 激活和/或 WAT 棕色化对新陈代谢的重要性,以及导致这些生热脂肪生物生成的方法,如寒冷暴露、甲状腺激素、体育锻炼、饮食和药理制剂(即 β3-肾上腺素能受体激动剂、胰高血糖素样肽 1、矿皮质激素受体拮抗剂、麻黄素)。这些刺激剂已显示出激活人体 BAT 的前景。我们的综述得出的结论是,在未来几年里,要更好地评估 BAT 激活对代谢健康(即无胰岛素抵抗和代谢综合征)的真正影响,并阐明围绕 BAT 生理的许多问题,使该器官确实成为预防和逆转肥胖和代谢紊乱的一个有吸引力的治疗靶点,还有许多障碍需要克服。
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来源期刊
Health sciences review (Oxford, England)
Health sciences review (Oxford, England) Medicine and Dentistry (General)
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75 days
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