Ectopic expression of RBP4 impairs the insulin pathway and inguinal fat deposition in mice

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ORIGINAL PAPER

Ectopic expression of RBP4 impairs the insulin pathway and inguinal fat deposition in mice Jia Cheng & Yuefeng Li & Guofang Wu & Jiameng Zheng & Hongzhao Lu & Xin’e Shi & Gongshe Yang

Received: 5 July 2013 / Accepted: 18 February 2014 / Published online: 4 March 2014 # University of Navarra 2014

Abstract A large body of evidence has linked retinolbinding protein 4 (RBP4) to systemic insulin resistance, but little is known about its function in fat deposition. This study aimed to confirm the involvement of RBP4 in inguinal fat deposition and insulin by intraperitoneal injection of adenovirus-mediated RBP4 to mice. Intraperitoneal injection of adenoviral vectors was validated as an efficient gene manipulation tool for overexpressing recombinant proteins in vivo. Ectopic expression of RBP4 decelerated inguinal fat deposition by decreasing the size of adipocytes. Moreover, the introduction of exogenous RBP4 blunted the response of inguinal adipocytes to insulin signals. These findings suggest that RBP4 impaired in vivo adipogenesis, partly through the repression of the insulin pathway. Keywords RBP4 . Adipokine . Inguinal fat deposition . Insulin sensitivity

J. Cheng : Y. Li : G. Wu : J. Zheng : H. Lu : X. Shi (*) : G. Yang (*) College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi 712100, China e-mail: [email protected] e-mail: [email protected] J. Cheng : H. Lu Vitamin D Research Institute, Shaanxi University of Technology, Hanzhong, Shaanxi 723000, China

Introduction The primary source of serum retinol-binding protein 4 (RBP4) in the physiological status is the liver [21], but RBP4 has recently emerged as a novel and controversial adipokine. Various clinical studies and correlation analyses have debated on whether adipose tissue-derived RBP4 is intrinsically associated with insulin resistance and obesity [14]. Two groups initially found that serum RBP4 level is positively correlated with body mass index in 2005 and 2006 [7, 24]. A single nucleotide polymorphism (SNP) in the RBP4 gene may produce high RBP4 levels and is possibly related to obesity [17]. The correlation between high RBP4 level and adiposity was observed in visceral adipose tissue studies [5, 11, 12]. Conversely, a significant decrease in weight caused by dietary control, exercise, or bariatric surgery reportedly accompanies low serum and adipose tissue levels of RBP4 and ameliorated insulin sensitivity [8, 10, 15]. However, some clinical investigations have not found the aforementioned relevance between the circulating RBP4 level and level of insulin resistance and obesity (adipose tissue amount and distribution) [3, 22]. Some studies also noted the absence of an existing correlation between serum RBP4 and adipose tissue RBP4 level [10, 13, 23, 25]. A previously prevailing explanation for this disparity was that elevated circulating RBP4 levels in type 2 diabetes (T2D) subjects can be a concomitant result of impaired renal clearance of RBP4, which is a by-product of T2D, caused by kidney failure [1, 9