用产热脂肪对抗肥胖:当前的挑战和进展。
Combating Obesity With Thermogenic Fat: Current Challenges and Advancements.
机构信息
Department of Nuclear Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, United States.
出版信息
Front Endocrinol (Lausanne). 2020 Apr 15;11:185. doi: 10.3389/fendo.2020.00185. eCollection 2020.
Brown fat and beige fat are known as thermogenic fat due to their contribution to non-shivering thermogenesis in mammals following cold stimulation. Beige fat is unique due to its origin and its development in white fat. Subsequently, both brown fat and beige fat have become viable targets to combat obesity. Over the last few decades, most therapeutic strategies have been focused on the canonical pathway of thermogenic fat activation via the β3-adrenergic receptor (AR). Notwithstanding, administering β3-AR agonists often leads to side effects including hypertension and particularly cardiovascular disease. It is thus imperative to search for alternative therapeutic approaches to combat obesity. In this review, we discuss the current challenges in the field with respect to stimulating brown/beige fat thermogenesis. Additionally, we include a summary of other newly discovered pathways, including non-AR signaling- and non-UCP1-dependent mechanisms, which could be potential targets for the treatment of obesity and its related metabolic diseases.
棕色脂肪和米色脂肪因其在哺乳动物受到冷刺激后对非颤抖性产热的贡献而被称为产热脂肪。米色脂肪因其起源和在白色脂肪中的发育而具有独特性。随后,棕色脂肪和米色脂肪都成为了对抗肥胖的可行靶点。在过去的几十年中,大多数治疗策略都集中在通过β3-肾上腺素能受体(AR)激活产热脂肪的经典途径上。然而,给予β3-AR 激动剂常常会导致副作用,包括高血压,特别是心血管疾病。因此,寻找替代的治疗方法来对抗肥胖症是至关重要的。在这篇综述中,我们讨论了目前在刺激棕色/米色脂肪产热方面的挑战。此外,我们还总结了其他新发现的途径,包括非 AR 信号和非 UCP1 依赖性机制,这些途径可能是治疗肥胖症及其相关代谢性疾病的潜在靶点。