Development of metabolic syndrome and functional state of mesenteric arteries in female rats fed a high-fat diet

BACKGROUND. Changes in the human nutrition profile have led to excessive consumption of fats and carbohydrates, which is accompanied by the development of metabolic syndrome (MS). The main studies of the mechanisms of MS are performed on males, the features of MS in females have not been sufficiently studied.

OBJECTIVE. The objective was to assess the state of lipid and carbohydrate metabolism, the functional state of the mesenteric arteries in intact and ovariectomized female Wistar rats under a high-fat dietary load.

MATERIALS AND METHODS. Four groups of female rats were used: HFD (high fat diet, n=14), intact, receiving 50% fat in the diet, HFD (n=14) — ovariectomized, receiving 50% fat, CG (n=12) — intact, receiving a standard diet, OvCG (n=12) — ovariectomized, receiving a standard diet. After 10 weeks, the responses of mesenteric arteries precontracted with phenylephrine to acetylcholine (ACh) in the absence and with the use of an NO synthase blocker (L-NAME), as well as to sodium nitroprusside (NP), were studied using microphoto- and video recording of the vessel diameter in vivo. The state of carbohydrate and lipid metabolism, arterial pressure (BP), and the level of visceral obesity were assessed. The study refers to an interventional single-sample controlled study.

RESULTS. In the absence of differences in body weight in HFD and OvHFD rats, excess fat intake leads to visceral obesity, increased triglyceride and LDL levels, increased blood pressure, and insulin resistance compared to CG and OvCG. Evaluation of mesenteric artery dilation at an ACh concentration of 10–5 mol/L showed that in HFD females the relaxation amplitude was 19.9% lower than in CG, and in OvHFD it was 21.3% lower than in OvCG. Compared with the magnitude of dilation on ACh without blockers, pre-incubation of vessels with L-NAME led to a decrease in the amplitude of ACh-induced vascular relaxation in CG by 68.0±3.6%, in OvCG by 70.1±3.4%, in HFD by 48.4±2.9%, in OvHFD by 55.1±3.9%. NP-induced vasodilation was reduced in HFD rats by 32.3%, in OvHFD by 32.2% compared with CG and OvCG.

CONCLUSION. Excessive fat consumption by female rats is accompanied by visceral obesity, increased blood pressure, dyslipidemia, and impaired carbohydrate metabolism, dyslipidemia. The development of MS is accompanied by endothelial dysfunction, manifested by a decrease in ACh-induced dilation due to both the suppression of NO production by the endothelium and a decrease in the sensitivity of SMC to NO, while in ovariectomized females, visceral obesity without a decrease in vascular reactivity compared to intact animals.

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