Berberine ameliorates mesenteric vascular dysfunction by modulating perivascular adipose tissue in diet-induced obese in rats

Berberine (BBR) has been found to have antiobesity effects, and obesity can lead to adipose tissue degeneration. As a special adipose tissue, perivascular adipose tissue (PVAT) is closely related to vascular function and affects vasoconstriction and relaxation. What happens to PVAT in the early stages of diet-induced obesity and how BBR affects vascular function is the focus of our experimental study.Sprague-Dawley rats were fed a high-fat diet (fat 34% kcal) for 4 weeks to simulate early obesity. Obese rats were treated with BBR (200 mg/kg) or metformin (MET, 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 analysed to indicate vascular function. Nitric oxide (NO) and noradrenaline (NA) release was quantified using an organ bath with fluorescence assays and ELISA, respectively. Network pharmacology was used to analyse the overlapping targets related to BBR and obesity-related diseases, and the expression of NOS in mesenteric PVAT was further analysed with immunohistochemistry and real-time PCR. The serum inflammatory factor levels were tested.BBR significantly reduced the levels of blood glucose, blood lipids and inflammatory factors in serum. It also effectively improved abnormal mesenteric vasoconstriction and relaxation in obese rats. There was no significant change in mesenteric vascular structure, but NO production and eNOS expression were significantly increased in mesenteric PVAT (P < 0.01), and NA was decreased (P < 0.05) in obese rats. All these changes in the mesenteric arterioles and PVAT of obese rats were reversed by treatment with BBR and MET.In diet-induced obesity in rats, the function of vasoconstriction and relaxation in mesenteric arterioles is altered, NO is increased, and NA is decreased in mesenteric PVAT. All these changes were reversed by BBR, suggesting a novel effect of BBR in ameliorating mesenteric vascular dysfunction by regulating PVAT.