Hong Hao, Xu Hou-Xi, Meng Jian-Zhong, Zhu Bing-Mei
Regenerative Medicine Research Center, West China Hospital, Sichuan University, Chengdu, China.
Key Laboratory of Acupuncture and Medicine Research of Ministry of Education, Nanjing University of Chinese Medicine, Nanjing, China.
Acupunct Med. 2022 Jun;40(3):249-257. doi: 10.1177/09645284211056345. Epub 2021 Dec 10.
Increasing evidence shows that miRNAs contribute to the establishment and development of obesity by affecting many biological and pathological processes, such as adipocyte differentiation, hepatic lipid metabolism, insulin resistance, and neurological regulation of obesity. As a clinical intervention approach, acupuncture has been shown to be effective in the treatment of obesity and other metabolic diseases. Our previous whole genome study in central nervous system (CNS)-specific 5 knockout (NKO) obese mice found that electroacupuncture (EA) could reduce body weight and promote white browning.
To clarify the effect of EA on miRNAs and understand how it regulates gene expression.
Twelve-week-old male 5NKO mice with body weight 20% greater than that of fl/fl (control) mice were divided into a 5NKO (model) group and EA-treated 5NKO + EA group. A cohort of 5fl/fl mice of the same age were included as the control group. EA was administered under isoflurane anesthesia at unilateral ST36 and ST44 daily (left and right sides were treated every other day), 6 times per week for a total of 4 weeks. The miRNA profile was generated and miRNA regulatory networks were analyzed in the 5 nestin-cre mice before and after EA treatment. Autophagy-related proteins in adipocytes were detected after over-expression of miR27a.
EA altered abnormal miRNA expression, including miRNA27a expression, and reduced the autophagy-related proteins ATG5 and ATG12.
We found that EA could regulate miRNA27a-mediated autophagy-related proteins and promote white fat browning, which may contribute to weight loss. To our knowledge, this is the first report of miRNAs potentially driving the effect of EA on white fat browning through the autophagy process.
越来越多的证据表明，微小RNA（miRNAs）通过影响许多生物学和病理过程，如脂肪细胞分化、肝脏脂质代谢、胰岛素抵抗和肥胖的神经调节，促进肥胖的发生和发展。作为一种临床干预方法，针灸已被证明对肥胖和其他代谢性疾病的治疗有效。我们之前在中枢神经系统（CNS）特异性5敲除（NKO）肥胖小鼠中的全基因组研究发现，电针（EA）可以减轻体重并促进白色脂肪棕色化。
阐明电针对miRNAs的影响，并了解其如何调节基因表达。
将体重比野生型（对照）小鼠重20%的12周龄雄性5NKO小鼠分为5NKO（模型）组和电针治疗的5NKO + EA组。将同一批12周龄的5fl/fl小鼠作为对照组。在异氟烷麻醉下，每天对单侧足三里（ST36）和三阴交（ST44）进行电针治疗（左右侧隔日交替治疗），每周6次，共4周。在电针治疗前后，对5只巢蛋白-cre小鼠进行微小RNA谱分析，并分析微小RNA调控网络。在miR27a过表达后，检测脂肪细胞中自噬相关蛋白。
电针改变了异常的微小RNA表达，包括miR27a的表达，并降低了自噬相关蛋白ATG5和ATG12的表达。
我们发现电针可以调节miR27a介导的自噬相关蛋白，并促进白色脂肪棕色化，这可能有助于减轻体重。据我们所知，这是首次报道微小RNA可能通过自噬过程驱动电针对白色脂肪棕色化的作用。
