Abstract
Insulin resistance (IR) plays a critical role in cardiovascular diseases and metabolic diseases. In this study, we identified the downregulation of DMRT2 in adipose tissues from insulin-resistant subjects through bioinformatics analysis and in an insulin-resistant mouse model through experimental analysis. DMRT2 overexpression significantly attenuated HDF-induced insulin resistance and inflammation in mice. Moreover, in control and insulin-resistant differentiated mouse 3T3-L1 adipocytes, DMRT2 overexpression attenuated but DMRT2 knockdown enhanced the insulin resistance of 3T3-L1 adipocytes. DMRT2 interacted with FXR and positively regulated FXR level and transcription activity. In both control and insulin-resistant differentiated mouse 3T3-L1 adipocytes, FXR knockdown enhanced the insulin resistance and attenuated the effects of DMRT2 overexpression upon 3T3-L1 adipocyte insulin resistance. In conclusion, we identify the downregulation of DMRT2 in the insulin-resistant mouse model and cell model. DMRT2 interacts with FXR and improves insulin resistance in adipocytes.
Highlights
Obesity is widely prevalent in the world
double-sex and mab-3-related transcription factor 2 (DMRT2) interacted with farnesoid X receptor (FXR) and positively regulated FXR level and transcription activity
According to GSE12050, DMRT2 expression was significantly downregulated in subcutaneous adipose tissue from subjects with obesity compared with non-obese (Figure S1C)
Summary
Obesity is widely prevalent in the world. Currently, 39% of the total population are overweight and 13% are obese [1, 2]. Adipose tissue remodeling is accompanied by extracellular matrix remodeling, inflammatory cell infiltration, abnormal adipokines, and free fatty acid secretion, which causes chronic inflammation, in turn leading to insulin resistance and to hypertension, atherosclerosis, coronary artery disease, and cardiovascular diseases [3]. Radin’s team injected free fatty acids in rats to cause insulin resistance in their skeletal muscles, which was partially improved in TLR4 knockout rats [9]. They indicated that high free fatty acid might be DMRT2 Improves Insulin Resistance the leading cause of insulin resistance due to obesity [9]. Understanding the mechanism of the occurrence and development of IR would provide new strategies to relieve IR and more effective therapies for metabolic diseases
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