Anti-inflammatory γ- and δ-tocotrienols improve cardiovascular, liver and metabolic function in diet-induced obese rats
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This study tested the hypothesis that γ- and δ-tocotrienols are more effective than α-tocotrienol and α-tocopherol in attenuating the signs of diet-induced metabolic syndrome in rats.
Five groups of rats were fed a corn starch-rich (C) diet containing 68 % carbohydrates as polysaccharides, while the other five groups were fed a diet (H) high in simple carbohydrates (fructose and sucrose in food, 25 % fructose in drinking water, total 68 %) and fats (beef tallow, total 24 %) for 16 weeks. Separate groups from each diet were supplemented with either α-, γ-, δ-tocotrienol or α-tocopherol (85 mg/kg/day) for the final 8 of the 16 weeks.
H rats developed visceral obesity, hypertension, insulin resistance, cardiovascular remodelling and fatty liver. α-Tocopherol, α-, γ- and δ-tocotrienols reduced collagen deposition and inflammatory cell infiltration in the heart. Only γ- and δ-tocotrienols improved cardiovascular function and normalised systolic blood pressure compared to H rats. Further, δ-tocotrienol improved glucose tolerance, insulin sensitivity, lipid profile and abdominal adiposity. In the liver, these interventions reduced lipid accumulation, inflammatory infiltrates and plasma liver enzyme activities. Tocotrienols were measured in heart, liver and adipose tissue showing that chronic oral dosage delivered tocotrienols to these organs despite low or no detection of tocotrienols in plasma.
In rats, δ-tocotrienol improved inflammation, heart structure and function, and liver structure and function, while γ-tocotrienol produced more modest improvements, with minimal changes with α-tocotrienol and α-tocopherol. The most important mechanism of action is likely to be reduction in organ inflammation.
KeywordsTocotrienols Tocopherols Cardiovascular Anti-inflammatory Metabolic syndrome Obesity
We thank Sime Darby Foods & Beverages Marketing Sdn. Bhd., Malaysia, for the supply of α-tocopherol, Davos Life Science Pte Ltd, Singapore, for the supply of α- and γ-tocotrienol, American River Nutrition, Inc., USA, for the supply of δ-tocotrienol, and The Malaysian Palm Oil Board for the supply of vitamin E-stripped palm olein. We thank Jason Brightwell, The Prince Charles Hospital, Brisbane, Australia, for the acquisition of echocardiographic images. We thank Suet Hoay Lee from Davos Life Science Pte Ltd, Singapore, and Ghazali Abdul Razak from The Malaysian Palm Oil Board for the HPLC analyses. We thank our colleagues R. Senthil Arun Kumar, Nikolas Jin Wang, Shazini Ramli, Maharshi Bhaswant, Hemant Poudyal and Sunil Panchal for technical assistance. Weng-Yew Wong and Lindsay Brown developed the original study aims; Weng-Yew Wong conducted the experiments and carried out the data analyses; data were interpreted by all authors. Leigh C. Ward assisted with dual-energy X-ray absorptiometry and provided nutritional advice. Chee Wai Fong and Wei Ney Yap assisted with detection and evaluation of vitamin E concentrations. Weng-Yew Wong and Lindsay Brown prepared manuscript drafts, with all authors contributing to the final version. Lindsay Brown has been the corresponding author throughout the writing process. This study was supported by the Strategic Research Fund of the University of Southern Queensland.
Compliance with ethical standards
Conflict of interest
The authors declare that there are no conflicts of interest.
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