Dataset Information

MiR-143-null Is against Diet-Induced Obesity by Promoting BAT Thermogenesis and Inhibiting WAT Adipogenesis.

ABSTRACT: Excessive energy intake is the main cause of obesity, and stimulation of brown adipose tissue (BAT) thermogenesis has emerged as an attractive tool for anti-obesity. Although miR-143 has been reported to promote white adipocyte differentiation, its role in BAT remains unclear. In our study, we found that during HFD-induced obesity, the expression of miR-143 in BAT was significantly reduced, and the expression of miR-143 in WAT first increased and then decreased. Knockout (KO) of miR-143 with CRISPR/Cas9 did not affect the energy metabolism of normal diet fed mice and brown adipocyte differentiation but inhibited the differentiation of white adipocytes. Importantly, during high fat diet-induced obesity, miR-143KO significantly reduced body weight, and improved energy expenditure, insulin sensitivity, and glucose tolerance. Further exploration showed that miR-143KO reduced the weight of adipose tissue, promoted mitochondrial number and functions, induced thermogenesis and lipolysis of BAT, increased lipolysis, and inhibited lipogenesis of white adipose tissue (WAT). Our study considerably improves our collective understanding of the function of miR-143 in adipose tissue and its potential significance in anti-obesity and provides a new avenue for the management of obesity through the inhibition of miR-143 in BAT and WAT.

SUBMITTER: Liu J

PROVIDER: S-EPMC9658130 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

miR-143-null Is against Diet-Induced Obesity by Promoting BAT Thermogenesis and Inhibiting WAT Adipogenesis.

Liu Jie J Liu Jiatao J Zeng Dewei D Wang Huan H Wang Yun Y Xiong Jiali J Chen Xingping X Luo Junyi J Chen Ting T Xi Qianyun Q Jiang Qingyan Q Zhang Yongliang Y

International journal of molecular sciences 20221027 21

Excessive energy intake is the main cause of obesity, and stimulation of brown adipose tissue (BAT) thermogenesis has emerged as an attractive tool for anti-obesity. Although miR-143 has been reported to promote white adipocyte differentiation, its role in BAT remains unclear. In our study, we found that during HFD-induced obesity, the expression of miR-143 in BAT was significantly reduced, and the expression of miR-143 in WAT first increased and then decreased. Knockout (KO) of miR-143 with CRI ...[more]

PMID: 36361843

Similar Datasets

Project description:Erythropoietin (EPO), clinically used as a hematopoietic drug, has received much attention due to its nonhematopoietic effects. EPO reportedly has beneficial effects on obesity and diabetes mellitus. We investigated whether interscapular brown adipose tissue (iBAT: main part of classical BAT) could play a role in EPO's anti-obesity and anti-diabetic effects in diet-induced obese mice. Four-week-old male C57BL/6J mice were fed a high-fat diet (HFD-Con), and half were additionally given an intraperitoneal injection of recombinant human EPO (200 IU/kg) (HFD-EPO) thrice a week for four weeks. At 8 weeks, EPO-injected mice showed significantly reduced body weight with reduced epididymal and subcutaneous white fat mass and unchanged caloric intake and locomotor activity. HOMA-IR (insulin resistance index) and glucose levels during intraperitoneal glucose tolerance test (IPGTT) were significantly lower in HFD-EPO mice than in HFD-Con mice. EPO-injected mice also showed increased oxygen consumption, indicative of metabolic rate, and skin temperature around iBAT tissue masses. EPO significantly upregulated the PRD1-BF1-RIZ1 homologous domain containing 16 (PRDM16), a transcriptional factor with a crucial role in brown adipocyte differentiation. EPO significantly increased phosphorylated signal transducer and activator of transcription 3 (STAT3), which is downstream of erythropoietin receptor (EpoR) and known to stabilize PRDM16. EPO's suppression of myocyte enhancer factor 2c (Mef2c) and microRNA-133a (miR-133a) via β3-adrenergic receptor caused PRDM16 upregulation. EPO-mediated enhancement of EpoR/STAT3 and β-adrenergic receptor/Mef2c/miR-133 pathways dramatically increases total uncoupling protein 1 (UCP1), an essential enzyme for BAT thermogenesis. Furthermore, EPO activated BAT's endocrine functions. EPO facilitated fibroblast growth factor 21 (FGF21) production and excretion in iBAT, associated with reduction of liver gluconeogenesis-related genes. Thus, EPO's improvement of obesity and glucose homeostasis can be attributed to increased iBAT thermogenic capacity and activation of BAT's endocrine functions.

Dataset Information

MiR-143-null Is against Diet-Induced Obesity by Promoting BAT Thermogenesis and Inhibiting WAT Adipogenesis.

Publications

miR-143-null Is against Diet-Induced Obesity by Promoting BAT Thermogenesis and Inhibiting WAT Adipogenesis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets