413-P: The Role of Retinol-Binding Protein 4 in the Regulation of Adipocyte Renin-Angiotensin System via Toll-Like Receptor 4

Objective: To explore the relationship between serum adipokine retinol binding protein 4 (RBP4) levels and essential hypertension as well as the role of RBP4 in activating adipocyte renin-angiotensin system (RAS) .

Methods: From December 2016 to March 2019, 96 essential hypertension patients without any anti-hypertensive drugs and 64 age- and gender-matched healthy subjects were recruited. Serum RBP4 was determined by enzyme linked immunosorbent assay (ELISA) . Mouse primary white adipocytes were exacted and treated with adenovirus carrying the expression sequence of RBP4 with or without Toll-like receptor 4 (TLR4) inhibitor TAK242. The level of Angiotensin II (Ang II) in the cell supernatant was measured by ELISA. Western Blot and qRT-PCR were used to detect the expression of adipocyte differentiation-related genes and key genes of RAS system.

Results: RBP4 was significantly higher in patients with essential hypertension [median (interquartile range) : 30.14 (23.76-40.65) ng/mL] than in healthy controls [25. (20.05-31.04) ng/mL] (P<0.01) . Multivariate logistic regression analysis showed that RBP4 was an independent risk factor for hypertension (OR=1.12, P=0.002) . In adipocytes, overexpression of RBP4 increased the expression of angiotensin converting enzyme, angiotensinogen, renin/angiotensin-forming enzyme 1 and Angiotensin II Receptor 1, as well as the secretion of Ang II (P<0.05) . Treatment of TLR4 inhibitor TAK242 alleviated RBP4 overexpression-induced activation of RAS system in adipocytes (P<0.05) .

Conclusions: Elevated serum RBP4 is associated with increased risk of essential hypertension. The mechanism might be related to the active effects of RBP4 on RAS system via TLR4 in adipocytes. [Keywords] retinol binding protein 4; essential hypertension; RAS system; adipocytes; Toll-like receptor 4