Reversine promotes browning of white adipocytes by suppressing miR‐133a

Abstract

Brown adipocytes are characterized by a high number of uncoupling protein 1 (UCP1)-positive mitochondrial content and increased thermogenic capacity. As UCP1-enriched cells can consume lipids by generating heat, browning of white adipocytes is now highlighted as a promising approach for the prevention of obesity and obesity-associated metabolic diseases. Upon cold exposure or β-adrenergic stimuli, downregulation of microRNA-133 (miR-133) elevates the expression levels of PR domain containing 16 (Prdm16), which has been shown to be a brown adipose determination factor, in brown adipose tissue and subcutaneous white adipose tissues (WAT). Here, we show that treatment of reversine to white adipocytes induces browning via suppression of miR-133a. Reversine treatment promoted the expression of brown adipocyte marker genes, such as Prdm16 and UCP1, increasing the mitochondrial content, while decreasing the levels of miR-133a and white adipocyte marker genes. Ectopic expression of miR-133a mimic reversed the browning effects of the reversine treatment. Moreover, intraperitoneal administration of reversine in mice upregulated thermogenesis and resulted in resistance to high-fat diet-mediated weight gain as well as browning of subcutaneous and epididymal WAT. Taken together, we found a novel way to promote browning of white adipocytes through downregulation of miR-133a followed by activation of Prdm16, with a synthetic chemical, reversine.

Hypoglycemic effect of the polysaccharides from Astragalus membranaceus on type 2 diabetic mice based on the “gut microbiota–mucosal barrier”

“…White adipose tissue is an important place for the body to store excess energy, and widely distributed in the subcutaneous layer and viscera of the body. 29 As shown in Fig. S3B, † the epididymal adipose index of mice in MC group was significantly higher than that of the NC group, and it could be decreased by 22.30% after supplementeation with APP.…”

Identification of Potential miRNA–mRNA Regulatory Network Associated with Pig Growth Performance in the Pituitaries of Bama Minipigs and Landrace Pigs

“…In addition, miR-4331 and miR-133a-3p jointly target BCL2L1 , a potent inhibitor of cell death promoting cell survival [ 37 ]. Furthermore, miR-133a-3p also promoted apoptosis and inhibited cell proliferation in a variety of cell lines [ 38 , 39 , 40 ].…”

Co-treatment with miR-21-5p inhibitor and Aurora kinase inhibitor reversine suppresses breast cancer progression by targeting sprouty RTK signaling antagonist 2

“…Evidence has shown that reversine can regulate several biological processes by inhibiting miRNAs. For example, reversine was found to promote browning of white adipocytes by downregulating miR-133a [ 50 ]. The role of reversine in the multipotency acquisition of myoblasts was also achieved through miR-133a silencing [ 51 ].…”