Tocotrienols reverse cardiovascular, metabolic and liver changes in high carbohydrate, high fat diet-fed rats

Abstract

Tocotrienols have been reported to improve lipid profiles, reduce atherosclerotic lesions, decrease blood glucose and glycated haemoglobin concentrations, normalise blood pressure in vivo and inhibit adipogenesis in vitro, yet their role in the metabolic syndrome has not been investigated. In this study, we investigated the effects of palm tocotrienol-rich fraction (TRF) on high carbohydrate, high fat diet-induced metabolic, cardiovascular and liver dysfunction in rats. Rats fed a high carbohydrate, high fat diet for 16 weeks developed abdominal obesity, hypertension, impaired glucose and insulin tolerance with increased ventricular stiffness, lower systolic function and reduced liver function. TRF treatment improved ventricular function, attenuated cardiac stiffness and hypertension, and improved glucose and insulin tolerance, with reduced left ventricular collagen deposition and inflammatory cell infiltration. TRF improved liver structure and function with reduced plasma liver enzymes, inflammatory cell infiltration, fat vacuoles and balloon hepatocytes. TRF reduced plasma free fatty acid and triglyceride concentrations but only omental fat deposition was decreased in the abdomen. These results suggest that tocotrienols protect the heart and liver, and improve plasma glucose and lipid profiles with minimal changes in abdominal obesity in this model of human metabolic syndrome.

Figure 1

Tail-cuff measurement of systolic blood pressure recorded at 0, 4, 8, 12 and 16 weeks for C, CT, H and HT diet-fed rats. Data shown as means ± SEM. Endpoint means with different letters in each data set are significantly different. n = 8/group.

Figure 2

Cumulative concentration-response curves for noradrenaline (A), sodium nitroprusside (B) and acetylcholine (C) in thoracic aortic rings from C, CT, H and HT-diet fed rats. Data shown as means ± SEM. Endpoint means with different letters in each data set significantly differ. n = 8/group.

Figure 3

Haematoxylin and eosin staining of left ventricle (20×) showing inflammatory cells (marked as “ic”) as dark spots outside the myocytes in C (A), CT (B), H (C) and HT (D) diet-fed rats. Picrosirius red staining of left ventricular interstitial collagen deposition (40×) in C (E), CT (F), H (G) and HT (H) diet-fed rats; collagen deposition is marked as “cd”.

Figure 4

Oral glucose (2 g/kg) (A) and insulin (0.33 IU/kg) (B) tolerance in C, CT, H and HT-diet fed groups. Data shown as means ± SEM. Endpoint means with different letters in each data set significantly differ. n = 8/group.

Figure 5

Haematoxylin and eosin staining of hepatocytes showing inflammatory cells around the portal region (marked as “ic”) (20×) in C (A), CT (B), H (C), and HT (D) diet-fed rats and hepatocytes with enlarged fat vacuole (marked as “fv”) (40×) and ballooned hepatocyte (marked as “bc”) in C (E), CT (F), H (G) and HT (H) diet-fed rats.