Tangeretin decreases insulin resistance, inflammatory state and oxidative stress in mice fed high-fat diet

Background: Tangeritin - TAN (4', 5, 6, 7, 8-pentamethoxyflavone) is a polymethoxyflavone isolated from the citrus fruits peels, which has potential to lower inflammation and oxidative stress. Previous studies have indicated that polymethoxyflavones have hypoglycemic effect and are capable of modulating anti-inflammatory adipokines, such as resistin, related to insulin resistance, and leptin, which regulates food intake and energy expenditure. These properties may have an impact on the reduction of obesity and its comorbidities, such as the metabolic syndrome.
Objective: The objective of this research was to evaluate the regulatory effects of TAN on metabolic syndrome risk factors in C57BL / 6J mice that mimic abdominal obesity and metabolic syndrome when exposed to a high fat diet.
Methods: Thirty-five mice were randomly divided into three groups with similar body weight distribution. In the control group (n = 10), the mice were fed a standard diet for 12 weeks. Experimental groups: Group 2 (n = 10) and Group 3 (n = 15) were fed a high-fat diet for 12 weeks. From the fifth week until the end of the experiment, Group 3 was daily supplemented with TAN (100mg / kg body weight) in the diet. The high-fat diet was used in the experimental groups to induce obesity and metabolic disorders related to the metabolic syndrome, such as abdominal obesity, hyperglycemia and hyperlipidemia. At the end of the experiment the animals were anesthetized and euthanized by cardiac puncture. Biochemical tests, oxidative stress evaluation and histology of adipose tissue were performed.
Results: It was verified that oral supplementation of TAN improved metabolic parameters altered by the high-fat diet in C57BL/6J mice. The group supplemented with TAN (Group 3) showed lower levels of glycemia and HOMA-IR index, compared to the Group 2, fed high-fat diet without TAN. Histological analysis showed that adipocytes areas were smaller in mice treated with TAN (Group 3) than in Group 2, fed high-fat diet only. Blood levels of leptin and resistin were elevated in Group 2 compared with Control. On the other hand, supplementation with TAN (Group 3) decreased blood levels of leptin and resistin compared to high-fat diet Group 2. Lipid peroxidation in the blood was twice as high in Group 2 as in Control, but was similar between TAN (Group 3) and Control group.
Discussion: Supplementation with tangeritin under high-fat diet improved cardiometabolic parameters related to the obesity and metabolic syndrome in this experimental model. In agreement with our results, previous studies have associated TAN with decrease of cardiometabolic risk factors, such as glucose intolerance and inflammatory markers, which contribute to the development of metabolic syndrome and type 2 diabetes mellitus.
Conclusion: Tangeretin supplementation was effective to treat cardiometabolic risk factors in mice previously fed high-fat diet.