MicroRNA‐146b promotes adipogenesis by suppressing the SIRT1‐FOXO1 cascade

• Published in: EMBO molecular medicine Vol. 5; no. 10; pp. 1602 - 1612
• Main Authors: Ahn, Jiyun, Lee, Hyunjung, Jung, Chang Hwa, Jeon, Tae Il, Ha, Tae Youl
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.10.2013; Blackwell Publishing Ltd; Springer Nature
• Subjects: 3T3-L1 Cells; Acetylation; adipogenesis; Adipogenesis - drug effects; Adipogenesis - genetics; Animals; Base Sequence; Down-Regulation; fat mass; Forkhead Box Protein O1; Forkhead Transcription Factors - metabolism; Gene Silencing; Intra-Abdominal Fat - diagnostic imaging; Intra-Abdominal Fat - physiology; Male; Mice; Mice, Inbred C57BL; Mice, Obese; MicroRNAs - antagonists & inhibitors; MicroRNAs - genetics; MicroRNAs - metabolism; MicroRNAs - pharmacology; microRNA‐146b; obesity; Obesity - genetics; Obesity - metabolism; Radiography; Research Article; RNA, Messenger - metabolism; Signal Transduction; SIRT1; Sirtuin 1 - antagonists & inhibitors; Sirtuin 1 - genetics; Sirtuin 1 - metabolism; Up-Regulation; adipogenesis; microRNA‐146b; SIRT1; obesity; fat mass; microRNA-146b
• ISSN: 1757-4676; 1757-4684
• DOI: 10.1002/emmm.201302647

Sirtuin 1 (SIRT1) plays a critical role in the maintenance of metabolic homeostasis and promotes fat mobilization in white adipose tissue. However, regulation of SIRT1 during adipogenesis, particularly through microRNAs, remains unclear. We observed that miR‐146b expression was markedly increased during adipogenesis in 3T3‐L1 cells. Differentiation of 3T3‐L1 was induced by overexpression of miR‐146b. Conversely, inhibition of miR‐146b decreased adipocyte differentiation. Bioinformatics‐based studies suggested that SIRT1 is a target of miR‐146b. Further analysis confirmed that SIRT1 was negatively regulated by miR‐146b. We also observed that miR‐146b bound directly to the 3′‐untranslated region of SIRT1 and inhibited adipogenesis through SIRT1 downregulation. The miR‐146b/SIRT1 axis mediates adipogenesis through increased acetylation of forkhead box O1 (FOXO1). Expression of miR‐146b was increased and SIRT1 mRNA subsequently decreased in the adipose tissues of diet‐induced and genetically obese mice. Furthermore, in vivo knockdown of miR‐146b by a locked nucleic acid miR‐146b antagomir significantly reduced body weight and fat volume in accordance with upregulation of SIRT1 and subsequent acetylation of FOXO1. Therefore, the miR‐146b/SIRT1 pathway could be a potential target for obesity prevention and treatment. Graphical Abstract miR‐146b is found here to regulate adipogenesis by targeting SIRT1 and increasing acetylated FOXO1. Inhibiting miR‐146b reduced body weight and fat mass in obese mice. This novel data indicate miR‐146b as a potential new target against obesity.