白色脂肪组织褐变的多方面调控及其治疗潜力。
The multifaceted regulation of white adipose tissue browning and their therapeutic potential.
作者信息
Satheesan Abhishek, Kumar Janardanan, Leela Kakithakara Vajravelu, Lathakumari Rahul Harikumar, Angelin Matcha, Murugesan Ria, Chaithanya Venkata
机构信息
Department of Microbiology, SRM Medical College Hospital and Research Centre, SRMIST, Chengalpattu, Kattankulathur, Tamil Nadu, 603203, India.
Department of General Medicine, SRM Medical College Hospital and Research Centre, SRMIST, Chengalpattu, Kattankulathur, Tamil Nadu, 603203, India.
出版信息
J Physiol Biochem. 2025 Aug 11. doi: 10.1007/s13105-025-01117-3.
Adipose tissue browning, the conversion of white adipose tissue (WAT) into brown or beige adipose tissue, offers potential for combating obesity and metabolic disorders. This review delves in to the transcriptional and epigenetic regulation of WAT browning and how it impacts metabolic health and its significance in various disease conditions. Further the review explains how various external factors such as diet and exercise play an influential role in the regulation of WAT browning. UCP1 gene, which plays a crucial role in cellular thermogenesis is found to be the major mediator of this phenomenon along with functional dynamics of mitochondria. Gut microbiome has been another focus point in this review that highlights how alterations to the composition of different species of bacteria in gut microbiome can directly influence WAT browning. Finally the review discusses the various pharmaceutical and neutraceutical options under research that targets WAT browning to improve metabolic status of an individual. Therapeutic strategies include β3-adrenergic receptor agonists, GLP-1 receptor agonists, AMPK activators, and natural compounds such as capsaicin and resveratrol. Emerging CRISPR/Cas9 gene therapies aim to induce WAT browning. Clinical evidence to prove the significance of this phenomena is currently limited but growing rapidly as seen in the number of clinical trials that are undergoing currently, therefore the review strongly rely upon animal model and cell culture based studies to justify this area of novel research. Despite its potential, challenges like individual variability, long-term safety, and complex gut microbiome interactions remain. Future research should target novel pathways, optimize therapeutic regimens, and personalize treatments.
脂肪组织褐变,即将白色脂肪组织(WAT)转化为棕色或米色脂肪组织,为对抗肥胖和代谢紊乱提供了潜力。本综述深入探讨了WAT褐变的转录和表观遗传调控,以及它如何影响代谢健康及其在各种疾病状态中的意义。此外,该综述还解释了饮食和运动等各种外部因素如何在WAT褐变的调控中发挥重要作用。在细胞产热中起关键作用的UCP1基因,连同线粒体的功能动态,被发现是这一现象的主要介导者。肠道微生物群是本综述的另一个重点,它强调了肠道微生物群中不同细菌种类组成的改变如何直接影响WAT褐变。最后,该综述讨论了正在研究的各种针对WAT褐变以改善个体代谢状态的药物和营养保健品选择。治疗策略包括β3-肾上腺素能受体激动剂、GLP-1受体激动剂、AMPK激活剂,以及辣椒素和白藜芦醇等天然化合物。新兴的CRISPR/Cas9基因疗法旨在诱导WAT褐变。目前证明这一现象重要性的临床证据有限,但随着当前正在进行的临床试验数量的增加,其数量正在迅速增长,因此该综述强烈依赖基于动物模型和细胞培养的研究来证明这一新型研究领域的合理性。尽管具有潜力,但个体差异、长期安全性和复杂的肠道微生物群相互作用等挑战仍然存在。未来的研究应针对新的途径,优化治疗方案,并实现个性化治疗。