Abstract
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.
Highlights
Obesity is an energy balance disorder in which nutrient intake chronically exceeds energy expenditure, resulting in the accumulation of white adipose tissue (Hofbauer, 2002)
Obesity is characterized by increased lipid storage in adipocytes and an increased number of adipocytes
Several miRNAs, including miR‐27a, miR‐130 and miR‐143, were previously shown to regulate adipogenesis. miR‐27a and miR‐130 suppress adipogenesis by inhibiting peroxisome proliferator‐activated receptor g (PPARg) (Kajimoto et al, 2006), whereas miR‐143 induces adipogenesis by downregulating ERK5 (Esau et al, 2004). These results suggest that miRNAs play important roles in regulating adipocyte differentiation
Summary
Obesity is an energy balance disorder in which nutrient intake chronically exceeds energy expenditure, resulting in the accumulation of white adipose tissue (Hofbauer, 2002). Epidemiological studies suggest that obesity accelerates atherosclerosis (McGill et al, 2002) and is an important predictor of cardiovascular disease (Hubert et al, 1983; Rimm et al, 1995). Increased adiposity is due to increases in the number and size of adipocytes, which leads to increased body fat and (1) Metabolism and Nutrition Research Group, Korea Food Research Institute, Seongnam, Korea (2) Division of Food Biotechnology, University of Science and Technology, Daejeon, Korea (3) Division of Animal Science, University of Chonnam National University, Gwangju, Korea. MiRNAs are important modulators of developmental and physiological processes, including energy homeostasis, lipid metabolism, pancreatic b‐cell development, adipogenesis and weight gain due to a high fat diet (Lin et al, 2009; Takanabe et al, 2008; Wienholds & Plasterk, 2005; Xu et al, 2003). MiRNAs in adipocytes have been shown to alter cell proliferation (the miR‐24‐1, miR‐31 and miR‐17‐92 cluster) (Sun et al, 2009; Wang et al, 2008), repress Wnt signalling (miR‐8) (Kennell et al, 2008), or repress peroxisome proliferator‐activated receptor g (PPARg; miR‐27a, miR‐27b and miR‐130) (Karbiener et al, 2009; Kim et al, 2010; Lin et al, 2009)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
