Naringin improves diet-induced cardiovascular dysfunction and obesity in high carbohydrate, high fat diet-fed rats

Abstract

Obesity, insulin resistance, hypertension and fatty liver, together termed metabolic syndrome, are key risk factors for cardiovascular disease. Chronic feeding of a diet high in saturated fats and simple sugars, such as fructose and glucose, induces these changes in rats. Naturally occurring compounds could be a cost-effective intervention to reverse these changes. Flavonoids are ubiquitous secondary plant metabolites; naringin gives the bitter taste to grapefruit. This study has evaluated the effect of naringin on diet-induced obesity and cardiovascular dysfunction in high carbohydrate, high fat-fed rats. These rats developed increased body weight, glucose intolerance, increased plasma lipid concentrations, hypertension, left ventricular hypertrophy and fibrosis, liver inflammation and steatosis with compromised mitochondrial respiratory chain activity. Dietary supplementation with naringin (approximately 100 mg/kg/day) improved glucose intolerance and liver mitochondrial dysfunction, lowered plasma lipid concentrations and improved the structure and function of the heart and liver without decreasing total body weight. Naringin normalised systolic blood pressure and improved vascular dysfunction and ventricular diastolic dysfunction in high carbohydrate, high fat-fed rats. These beneficial effects of naringin may be mediated by reduced inflammatory cell infiltration, reduced oxidative stress, lowered plasma lipid concentrations and improved liver mitochondrial function in rats.

Figure 1

Effect of naringin on systolic blood pressure. Time course of tail cuff systolic blood pressure of Wistar rats given C, CN, H and HN (n = 9 in each group). Means without a common letter are significantly different at p < 0.05.

Figure 2

Hematoxylin and eosin staining of left ventricular tissue showing inflammatory cell infiltration of C (A), CN (B) H (C), HN (D) (upper panel); ic, inflammatory cell. Picrosirius red staining for left ventricular tissue collagen of C (E), CN (F), H (G), HN (H); fb, collagen deposition (lower panel).

Figure 3

Cumulative concentration-response curves for noradrenaline (A), sodium nitroprusside (B) and acetylcholine (C) in thoracic aortic rings derived from C, CN, H and HN treated groups. All concentrations are expressed as log concentration (mol/L). Data are shown as the mean ± SEM, n = 8.

Figure 4

Haematoxylin and eosin staining of liver (×20) showing fat deposition in C (A), CN (B) H (C), HN (D) rats (fd, fat droplets; pv, portal vein (upper panel)) and ×40 for C (E), CN (F) H (G), HN (H) rats (middle panel). Milligan’s trichrome staining of the liver section (×20) showing collagen as darker blue region in C (E), CN (F), H (G), HN (H) rats; pvc, portal vein collagen (lower panel).