Department of Obstetrics and Gynecology, David Geffen School of Medicine, University of California Los Angeles (UCLA), Los Angeles, CA 90095, USA.
Division of Endocrinology and Metabolism, Charles R Drew University of Medicine and Science, Los Angeles, CA 90059, USA.
Cells. 2021 Nov 5;10(11):3030. doi: 10.3390/cells10113030.
Obesity-associated metabolic abnormalities comprise a cluster of conditions including dyslipidemia, insulin resistance, diabetes and cardiovascular diseases that has affected more than 650 million people all over the globe. Obesity results from the accumulation of white adipose tissues mainly due to the chronic imbalance of energy intake and energy expenditure. A variety of approaches to treat or prevent obesity, including lifestyle interventions, surgical weight loss procedures and pharmacological approaches to reduce energy intake and increase energy expenditure have failed to substantially decrease the prevalence of obesity. Brown adipose tissue (BAT), the primary source of thermogenesis in infants and small mammals may represent a promising therapeutic target to treat obesity by promoting energy expenditure through non-shivering thermogenesis mediated by mitochondrial uncoupling protein 1 (UCP1). Since the confirmation of functional BAT in adult humans by several groups, approximately a decade ago, and its association with a favorable metabolic phenotype, intense interest on the significance of BAT in adult human physiology and metabolic health has emerged within the scientific community to explore its therapeutic potential for the treatment of obesity and metabolic diseases. A substantially decreased BAT activity in individuals with obesity indicates a role for BAT in the setting of human obesity. On the other hand, BAT mass and its prevalence correlate with lower body mass index (BMI), decreased age and lower glucose levels, leading to a lower incidence of cardio-metabolic diseases. The increased cold exposure in adult humans with undetectable BAT was associated with decreased body fat mass and increased insulin sensitivity. A deeper understanding of the role of BAT in human metabolic health and its interrelationship with body fat distribution and deciphering proper strategies to increase energy expenditure, by either increasing functional BAT mass or inducing white adipose browning, holds the promise for possible therapeutic avenues for the treatment of obesity and associated metabolic disorders.
肥胖相关的代谢异常包括血脂异常、胰岛素抵抗、糖尿病和心血管疾病等多种病症，这些病症已经影响到了全球超过 6.5 亿人。肥胖是由于白色脂肪组织的积累，主要是由于能量摄入和消耗的长期失衡所致。目前已经有多种治疗或预防肥胖的方法，包括生活方式干预、手术减肥程序以及减少能量摄入和增加能量消耗的药物方法，但这些方法都未能显著降低肥胖的流行率。棕色脂肪组织（BAT）是婴儿和小型哺乳动物产热的主要来源，通过解偶联蛋白 1（UCP1）介导的非寒战产热来促进能量消耗，这可能代表着一种有前途的治疗肥胖的治疗靶点。自从大约十年前，几个研究小组证实了成年人体内功能性 BAT 的存在，并发现其与良好的代谢表型有关之后，科学界对 BAT 在成年人体生理学和代谢健康中的意义产生了浓厚的兴趣，以探索其在治疗肥胖和代谢疾病方面的治疗潜力。肥胖个体中 BAT 活性的显著降低表明 BAT 在人类肥胖症的发生中起着作用。另一方面，BAT 质量及其患病率与较低的体重指数（BMI）、较低的年龄和较低的血糖水平相关，这导致了较低的心脑血管疾病发病率。在未检测到 BAT 的成年人群中，增加寒冷暴露与体脂肪量减少和胰岛素敏感性增加有关。深入了解 BAT 在人类代谢健康中的作用及其与体脂肪分布的相互关系，并制定适当的策略来增加能量消耗，无论是通过增加功能性 BAT 质量还是诱导白色脂肪褐变，都为治疗肥胖症和相关代谢紊乱提供了可能的治疗途径。
