Jiang Na, Yang Ming, Han Yachun, Zhao Hao, Sun Lin
Hunan Key Laboratory of Kidney Disease and Blood Purification, Department of Nephrology, The Second Xiangya Hospital of Central South University, Changsha, China.
Front Pharmacol. 2022 Apr 8;13:870250. doi: 10.3389/fphar.2022.870250. eCollection 2022.
Given that obesity and diabetes have been major public health concerns and that disease morbidities have been rising continuously, effective treatment for these diseases is urgently needed. Because adipose tissue metabolism is involved in the progression of obesity and diabetes, it might be efficient to target adipocyte metabolic pathways. Positive regulatory domain zinc finger region protein 16 (PRDM16), a transcription factor that is highly expressed in adipocytes, plays a key role in adipose tissue metabolism, such as the browning and thermogenesis of adipocytes, the beigeing of adipocytes, the adipogenic differentiation of myoblasts, and the conversion of visceral adipocytes to subcutaneous adipocytes. Furthermore, clinical and basic studies have shown that the expression of PRDM16 is associated with obesity and diabetes and that PRDM16 signaling participates in the treatment of the two diseases. For example, metformin promotes thermogenesis and alleviates obesity by activating the AMPK/αKG/PRDM16 signaling pathway; rosiglitazone alleviates obesity under the synergistic effect of PRDM16; resveratrol plays an antiobesity role by inducing the expression of PRDM16; liraglupeptide improves insulin resistance by inducing the expression of PRDM16; and mulberry leaves play an anti-inflammatory and antidiabetes role by activating the expression of brown fat cell marker genes (including PRDM16). In this review, we summarize the evidence of PRDM16 involvement in the progression of obesity and diabetes and that PRDM16 may be a promising therapy for obesity and diabetes.
鉴于肥胖和糖尿病一直是主要的公共卫生问题，且疾病发病率持续上升，迫切需要针对这些疾病的有效治疗方法。由于脂肪组织代谢参与肥胖和糖尿病的进展，靶向脂肪细胞代谢途径可能是有效的。正调控域锌指区蛋白16（PRDM16）是一种在脂肪细胞中高度表达的转录因子，在脂肪组织代谢中起关键作用，如脂肪细胞的褐变和产热、脂肪细胞的米色化、成肌细胞的脂肪生成分化以及内脏脂肪细胞向皮下脂肪细胞的转化。此外，临床和基础研究表明，PRDM16的表达与肥胖和糖尿病相关，且PRDM16信号通路参与这两种疾病的治疗。例如，二甲双胍通过激活AMPK/αKG/PRDM16信号通路促进产热并减轻肥胖；罗格列酮在PRDM16的协同作用下减轻肥胖；白藜芦醇通过诱导PRDM16的表达发挥抗肥胖作用；利拉鲁肽通过诱导PRDM16的表达改善胰岛素抵抗；桑叶通过激活棕色脂肪细胞标记基因（包括PRDM16）的表达发挥抗炎和抗糖尿病作用。在本综述中，我们总结了PRDM16参与肥胖和糖尿病进展的证据，以及PRDM16可能是肥胖和糖尿病的一种有前景的治疗方法。
