Department of Endocrinology, Endocrinology Research Center, Xiangya Hospital of Central South University, Changsha, China.
Department of Biochemistry and Molecular Biology, Hunan University of Chinese Medicine, Changsha, China.
Aging Cell. 2020 Jan;19(1):e13077. doi: 10.1111/acel.13077. Epub 2019 Nov 25.
With the increasing aging population, aging-associated diseases are becoming epidemic worldwide, including aging-associated metabolic dysfunction. However, the underlying mechanisms are poorly understood. In the present study, we aimed to investigate the role of microRNA miR-188 in the aging-associated metabolic phenotype. The results showed that the expression of miR-188 increased gradually in brown adipose tissue (BAT) and inguinal white adipose tissue (iWAT) of mice during aging. MiR-188 knockout mice were resistant to the aging-associated metabolic phenotype and had higher energy expenditure. Meanwhile, adipose tissue-specific miR-188 transgenic mice displayed the opposite phenotype. Mechanistically, we identified the thermogenic-related gene Prdm16 (encoding PR domain containing 16) as the direct target of miR-188. Notably, inhibition of miR-188 expression in BAT and iWAT of aged mice by tail vein injection of antagomiR-188 ameliorated aging-associated metabolic dysfunction significantly. Taken together, our findings suggested that miR-188 plays an important role in the regulation of the aging-associated metabolic phenotype, and targeting miR-188 could be an effective strategy to prevent aging-associated metabolic dysfunction.
随着人口老龄化的增加，与衰老相关的疾病在全球范围内流行，包括与衰老相关的代谢功能障碍。然而，其潜在机制尚不清楚。在本研究中，我们旨在研究 microRNA miR-188 在与衰老相关的代谢表型中的作用。结果表明，miR-188 的表达在小鼠衰老过程中逐渐增加，在棕色脂肪组织 (BAT) 和腹股沟白色脂肪组织 (iWAT) 中增加。miR-188 敲除小鼠对与衰老相关的代谢表型具有抗性，并且具有更高的能量消耗。同时，脂肪组织特异性 miR-188 转基因小鼠表现出相反的表型。从机制上讲，我们确定了与产热相关的基因 Prdm16（编码 PR 结构域包含 16）为 miR-188 的直接靶标。值得注意的是，通过尾静脉注射 antagomiR-188 抑制衰老小鼠 BAT 和 iWAT 中 miR-188 的表达显著改善了与衰老相关的代谢功能障碍。总之，我们的研究结果表明，miR-188 在调节与衰老相关的代谢表型中发挥着重要作用，靶向 miR-188 可能是预防与衰老相关的代谢功能障碍的有效策略。
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