MiR-143 Targets SYK to Regulate NEFA Uptake and Contribute to Thermogenesis in Male Mice

Author:

Liu Jie123ORCID,Wei Limin23,Chen Ting1,Wang Huan1,Luo Junyi1,Chen Xingping14,Jiang Qingyan1,Xi Qianyun1,Sun Jiajie1,Zhang Lin1ORCID,Zhang Yongliang1ORCID

Affiliation:

1. Guangdong Provincial Key Laboratory of Animal Nutrition Control, College of Animal Science, South China Agricultural University , Guangzhou, Guang-dong 510642 , China

2. Sanya Institute, Hainan Academy of Agricultural Sciences (Hainan Experi-mental Animal Research Center) , Sanya, Hainan 572000 , China

3. Institute of Animal Husbandry and Veterinary Medicine, Hainan Academy of Agricultural Sciences, Hainan Key Laboratory for Tropical Animal Breeding and Disease Research , Haikou, Hainan 571100 , China

4. Jiangxi Province Key Laboratory of Animal Nutrition, College of Animal Science and Technology, Jiangxi Agricultural University , Nanchang 330045 , China

Abstract

Abstract Excessive energy intake is the main cause of obesity, and stimulation of brown adipose tissue (BAT) and white adipose tissue (WAT) thermogenesis has emerged as an attractive tool for antiobesity. Although miR-143 has been reported to be associated with BAT thermogenesis, its role remains unclear. Here, we found that miR-143 had highest expression in adipose tissue, especially in BAT. During short-term cold exposure or CL316,243 was injected, miR-143 was markedly downregulated in BAT and subcutaneous WAT (scWAT). Moreover, knockout (KO) of miR-143 increases the body temperature of mice upon cold exposure, which may be due to the increased thermogenesis of BAT and scWAT. More importantly, supplementation of miR-143 in BAT of KO mice can inhibit the increase in body temperature in KO mice. Mechanistically, spleen tyrosine kinase was revealed for the first time as a new target of miR-143, and deletion of miR-143 facilitates fatty acid uptake in BAT. In addition, we found that brown adipocytes can promote fat mobilization of white adipocytes, and miR-143 may participate in this process. Meanwhile, we demonstrate that inactivation of adenylate cyclase 9 (AC9) in BAT inhibits thermogenesis through AC9–PKA–AMPK–CREB–UCP1 signaling pathway. Overall, our results reveal a novel function of miR-143 on thermogenesis, and a new functional link of the BAT and WAT.

Funder

Sanya Yazhou Bay Science and Technology City

Chinese Academy of Agricultural Sciences

National Natural Science Foundation of China

Publisher

The Endocrine Society

Subject

Endocrinology

Cited by 2 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

1. Pulling the trigger: Noncoding RNAs in white adipose tissue browning;Reviews in Endocrine and Metabolic Disorders;2023-12-29

2. The Ketogenic Effect of SGLT-2 Inhibitors—Beneficial or Harmful?;Journal of Cardiovascular Development and Disease;2023-11-16

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