Berberine ameliorate mesenteric vascular dysfunction by perivascular adipose tissue on diet-induced obesity rats

Abstract

Background Berberine has been found to have anti-obesity effects, and obesity can lead to adipose tissue degeneration. As a special adipose tissue, perivascular adipose tissue (PVAT) is closely related to vascular function. What happens to PVAT in diet-induced obesity and how it affects vascular function are the focus of our experimental study. Methods Sprague-Dawley rats were fed with high fat diet (fat 34% kcal) for 4 weeks, simulated early obesity model. Obesity rats were treated with BBR (200 mg/kg) or metformin (100 mg/kg) by gavage for 2 weeks. The mesenteric arterioles were studied by atomic force microscopy (AFM), the Force vs time curves were observed and analyzed to indicate vascular function. Nitric oxide (NO) and noradrenaline (NA) released were quantified using organ bath with fluorescence assays and ELISA, respectively. Using network pharmacology to analyze the overlapping targets related of BBR and obesity-related diseases, and further analyzes the expression of NOS in mesenteric perivascular adipose tissue (PVAT) with immunohistochemistry and real-time PCR. The serum inflammatory factors levels were tested. Results BBR could significantly reduce the levels of blood glucose, blood lipid and inflammatory factors in serum, and effectively improved the abnormal mesenteric vasoconstriction and relaxation in obesity rats. There was no significant change in mesenteric vascular structure in obesity rats, but collagen fibers in mesenteric tissue were increased, and NO production and eNOS expression in mesenteric PVAT were increase, NA was decrease. All these changes in obesity rats on mesenteric tissue and PVAT were reversed by treated with BBR and metformin. Conclusions In diet-induced obesity rats, the function of vasoconstriction and relaxation in mesenteric arterioles are altered, NO is increased but NA is decreased in mesenteric PVAT. All these changes are reversed by BBR, suggesting a novel effects of BBR ameliorate mesenteric vascular dysfunction through regulating the PVAT, which may closely relate with anti-inflammatory and against oxidative stress effects.