STEAP4 and insulin resistance
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REVIEW
STEAP4 and insulin resistance Xiaoling Chen • Zhiqing Huang • Bo Zhou • Huan Wang • Gang Jia • Guangmang Liu • Hua Zhao
Received: 18 November 2013 / Accepted: 26 February 2014 Ó Springer Science+Business Media New York 2014
Abstract Obesity is a multifactorial disease that caused by the interactions between genetic susceptibility genes and environmental cues. Obesity is considered as a major risk factor of insulin resistance. STEAP4 is a novel antiobesity gene that is significantly down-regulated in adipose tissue of obese patients. Over-expression of STEAP4 can improve glucose uptake and mitochondrial function, and increase insulin sensitivity. STEAP4 expression is regulated by a variety of inflammatory cytokines, hormones, or adipokines. In this review, we discuss function of STEAP4 in regulating insulin resistance in adipose tissue in vivo, as well as in adipocytes in vitro. Keywords STEAP4 Insulin resistance Glucose uptake Mitochondrial function Inflammation Signal pathway
Introduction Obesity is an increasingly prevalent public health issue that is usually associated with insulin resistance (IR), type 2 diabetes, hypertension, and coronary heart disease
X. Chen Z. Huang (&) B. Zhou H. Wang G. Jia G. Liu H. Zhao Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu 611130, Sichuan, People’s Republic of China e-mail: [email protected]
[1, 2]. At early onset of obesity, macrophages infiltrate into expanding adipose tissue and secrete proinflammatory cytokines, such as TNFa, IL-6, MCP-1, and IL-1b [3–6]. Therefore, identification of the genes defect in obesity would not only help to elucidate the underlying mechanisms of the obesity, but also be important for therapeutic treatment of obesity and its-associated pathogenesis. Six-transmembrane epithelial antigen of prostate 4 (STEAP4), also known as six-transmembrane protein of prostate 2 (STAMP2) or TNF-induced adipose-related protein (TIARP), belongs to the STEAP protein family and the metalloreductases family [7]. The STEAP4 counteracts the inflammation and insulin resistance in adipocytes and its expression level was significantly down-regulated in obese patients [8–10] and diabetic ApoE-/-/LDLR-/mice [11]. On contrary, recent studies reported that STEAP4 levels in both subcutaneous (sc) and visceral adipose tissue (VAT) were upregulated in obesity [12, 13]. The expression of STEAP4 was tightly controlled by inflammatory cytokines or adipokines, including TNFa, IL6, IL-1b, and leptin in adipocytes [14–16], and it was highly induced in human adipocytes differentiated in the presence of 1,25-dihydroxyvitamin D3 [17]. STEAP4 knockdown led to inhibition of adipogenesis by diminishing the expression of CCAAT/enhancer binding protein alpha (C/EBPa) and peroxisome proliferator-activated receptor gamma (PPARc) [18]. In addition, a previous study demonstrated that the STEAP4 gene expression was regulated by some insulin resistance
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