Abstract
Tocotrienols (T3s) are a subclass of unsaturated vitamin E that have been extensively studied for their anti-proliferative, anti-oxidative and anti-inflammatory properties in numerous cancer studies. Recently, T3s have received increasing attention due to their previously unrecognized property to attenuate obesity and its associated metabolic complications. In this review, we comprehensively evaluated the recent published scientific literature about the influence of T3s on obesity, with a particular emphasis on the signaling pathways involved. T3s have been demonstrated in animal models or human subjects to reduce fat mass, body weight, plasma concentrations of free fatty acid, triglycerides and cholesterol, as well as to improve glucose and insulin tolerance. Their mechanisms of action in adipose tissue mainly include (1) modulation of fat cell adipogenesis and differentiation; (2) modulation of energy sensing; (3) induction of apoptosis in preadipocytes and (4) modulation of inflammation. Studies have also been conducted to investigate the effects of T3s on other targets, e.g., the immune system, liver, muscle, pancreas and bone. Since δT3 and γT3 are regarded as the most active isomers among T3s, their clinical relevance to reduce obesity should be investigated in human trials.
Highlights
According to the World Health Organization (WHO), obesity is defined as abnormal or excessive fat accumulation that may impair health
Found that rats fed with a T3 mixture (33.9% αT3, 47.1% γT3 and 11% δT3) for six weeks followed by a vitamin E-depleted diet for one month, the αT3 and γT3 concentrations remained high in adipose tissue, indicating that αT3 and γT3 have slow degradation rates and that adipose tissue is a unique site to store T3s [56]
Consistent with the results from 3T3-L1 cells, our research has identified the inhibitory effects of γT3 on adipogenesis by using primary human adipose tissue-derived stem cells, a physiologically more relevant adipocyte model to human than 3T3-L1 preadipocytes derived from rodents [75,76]
Summary
According to the World Health Organization (WHO), obesity is defined as abnormal or excessive fat accumulation that may impair health. T3s are being actively investigated for their preventive or therapeutic roles in some cancers, T3s have received less attention as dietary strategies to reduce obesity and its associated metabolic complications than their saturated counterpart. It has been reported that T3s reduce body weight [16] and improve plasma glucose and lipid hepato-protective effects in adults with nonalcoholic fatty liver disease [17], which is a complication associated with obesity. The pharmacological function and therapeutic potential of T3s to attenuate metabolic syndromes, such as cardiovascular disease, diabetes and lipid disorder, have been recognized and reviewed by several researchers [18,19]. Despite several review articles showing that T3s exert anti-cancer effects on various cell types via modifying multiple signaling pathways, only scattered information is available regarding the mechanism of action of T3s in regulating obesity. We focus on delta, gamma and mixed isomers of T3s rather than alpha and beta analogs based on stronger anti-obesity effects observed in γ and δT3
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