^|^gamma;-Tocotrienol Attenuates Triglyceride through Effect on Lipogenic Gene Expressions in Mouse Hepatocellular Carcinoma Hepa 1-6

Burdeos, Gregor Carpentero; Nakagawa, Kiyotaka; Watanabe, Akio; Kimura, Fumiko; Miyazawa, Teruo

doi:10.3177/jnsv.59.148

Cited by 19 publications

(18 citation statements)

References 14 publications

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“…The anti-obesity effects of T3 have also been demonstrated in in vitro studies [331][332][333] and obese animal models [41,102,103,314,316,334]. T3 suppressed adipogenesis with the decrease of intracellular TG level and lipid droplets in mouse hepatoma Hepa 1-6 cells [40], human hepatoma HepG2 cells [41,47], 3T3-L1 murine preadipocytes [331,335], 3T3-F442A murine preadipocytes [336], and primary human adipose-derived stem cells [317,332]. The potency of anti-adipogenic activities of T3 follows the rank order of γ > δ > β > α [331,332].…”

Section: Effects Of Tocotrienol On Obesity Diabetes and Their Complmentioning

confidence: 79%

“…T3 decreased fatty acid synthase (FAS), sterol regulatory element-binding protein (SREBP), stearoyl-coenzyme A desaturase 1 (SCD1), and elevating carnitine palmitoyltransferase 1A (CPT1A) gene expression in mouse hepatocellular carcinoma (Hepa 1-6) cells. However, the cholesterol level remained unchanged [40]. In another study, supplementation of 10-15 µM γT3 suppressed cellular accumulation of TG in human hepatocellular carcinoma (HepG2) cells, especially those cultured in fat-loaded medium [41].…”

Section: Effects Of Tocotrienol On Lipid Metabolismmentioning

confidence: 95%

“…Many in vitro studies examining the mechanism of action of T3 in reducing hypercholesterolemia have been conducted. Triglyceride (TG) synthesis could be lowered by T3 via modulating lipogenic gene expression based on cellular studies [40]. T3 decreased fatty acid synthase (FAS), sterol regulatory element-binding protein (SREBP), stearoyl-coenzyme A desaturase 1 (SCD1), and elevating carnitine palmitoyltransferase 1A (CPT1A) gene expression in mouse hepatocellular carcinoma (Hepa 1-6) cells.…”

Section: Effects Of Tocotrienol On Lipid Metabolismmentioning

confidence: 99%

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Potential Role of Tocotrienols on Non-Communicable Diseases: A Review of Current Evidence

et al. 2020

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Tocotrienol (T3) is a subfamily of vitamin E known for its wide array of medicinal properties. This review aimed to summarize the health benefits of T3, particularly in prevention or treatment of non-communicable diseases (NCDs), including cardiovascular, musculoskeletal, metabolic, gastric, and skin disorders, as well as cancers. Studies showed that T3 could prevent various NCDs, by suppressing 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) in the mevalonate pathway, inflammatory response, oxidative stress, and alternating hormones. The efficacy of T3 in preventing/treating these NCDs is similar or greater compared to tocopherol (TF). TF may lower the efficacy of T3 because the efficacy of the combination of TF and T3 was lower than T3 alone in some studies. Data investigating the effects of T3 on osteoporosis, arthritis, and peptic ulcers in human are limited. The positive outcomes of T3 treatment obtained from the preclinical studies warrant further validation from clinical trials.Nutrients 2020, 12, 259 2 of 84 Nutrients 2020, 12, 259 4 of 84 the order δ > γ > β > α [45]. Using HepG2 cells, γT3 was shown to stimulate apolipoprotein B (Apo-B) degradation by decreasing its translocation into the endoplasmic reticulum (ER) lumen. This action eventually caused a reduction in the number of Apo-B in lipoprotein particles [46]. Other reports showed that γT3 and δT3 had the potential to reduce the hepatic TG synthesis and very-low-density lipoprotein (VLDL) secretion by suppressing expression of genes involved in lipid homeostasis, particularly the TG, cholesterol, and VLDL biosynthesis. Moreover, δT3 also promoted the efflux of LDL through LDL receptor expression [47]. A summary of the literature on effect of T3 supplementation on lipid profile of hypercholesterolemic model in vitro is shown in Table 1.Animal models of dyslipidemia have been used to investigate the effects of T3 on lipid profile. Several animals have been tested, including chicken, swine and rodents (rats, hamsters, guinea pigs). In chickens fed with a varying level of αTF and γT3, Qureshi et al. (1996) showed that αTF enhanced the inhibition of HMGCR by γT3. They further stipulated that the vitamin E mixture should contain 15-20% of αTF and approximately 60% of γT3 or δT3 for optimal anti-cholesterol effects [48]. In the subsequent study, demonstrated that combination of 50 ppm T3-rich fraction (TRF) and 50 ppm lovastatin was more effective in suppressing HMGCR activity compared to lovastatin alone in chickens. The combination also reduced serum TC and LDL-C, TG, Apo-B, thromboxane B 2 , and platelet factor 4 in contrast to individual treatment [49]. Using chicken supplemented with 50 ppm of δT3, Qureshi et al. (2011) further revealed that δT3 reduced TC and LDL-C besides suppressing the lipid elevating effects of dexamethasone and potentiated the TG-lowering effect of riboflavin [50]. Using genetically hypercholesterolemic swine, Qureshi et al. (1991) demonstrated the significant effect of TRF in lowering serum TC, LDL-C, Apo-B, thrombo...

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Section: Effects Of Tocotrienol On Obesity Diabetes and Their Complmentioning

confidence: 79%

Section: Effects Of Tocotrienol On Lipid Metabolismmentioning

confidence: 95%

Section: Effects Of Tocotrienol On Lipid Metabolismmentioning

confidence: 99%

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Potential Role of Tocotrienols on Non-Communicable Diseases: A Review of Current Evidence

et al. 2020

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“…Recently, biological mechanisms for the activity of tocotrienols against hepatic triglycerides accumulation have been reported. It has been shown that gamma-tocotrienol, but not alpha-tocopherol, was able to attenuate triglycerides accumulation by regulating fatty acid syntase and carnitine palmitoyltransferase leading to a reduction of hepatic inflammation and endoplasmic reticulum stress [21,22]. A 16-week study on rats fed high fat and high carbohydrate diet, showed a reduction of the hepatic fatty changes with “normalised portal inflammatory cells” [23].…”

Section: Discussionmentioning

confidence: 99%

Tocotrienols for normalisation of hepatic echogenic response in nonalcoholic fatty liver: a randomised placebo-controlled clinical trial

Magosso

Ansari

Gopalan

et al. 2013

Nutr J

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BackgroundNonalcoholic fatty liver disease (NAFLD) is one of the commonest liver disorders. Obesity, insulin resistance, lipid peroxidation and oxidative stress have been identified amongst the possible hits leading to the onset and progression of this disease. Nutritional evaluation of NAFLD patients showed a lower-than-recommended intake of vitamin E. Vitamin E is a family of 8 isoforms, 4 tocopherols and 4 tocotrienols. Alpha-tocopherol has been widely investigated in liver diseases, whereas no previous clinical trial has investigated tocotrienols for NAFLD. Aim of the study was to determine the effects of mixed tocotrienols, in normalising the hepatic echogenic response in hypercholesterolaemic patients with ultrasound-proven NAFLD.MethodsEighty-seven untreated hypercholesterolaemic adults with ultrasound-proven NAFLD were enrolled and randomised into control group (n = 44) and tocotrienols group (n = 43). The treatment, either mixed tocotrienols 200 mg twice daily or placebo, had a 1-year duration.Normalisation of hepatic echogenic response, being the trial primary aim, was used in sample size calculations. The data were assessed according to intention to treat principle as primary outcome. Per protocol analysis was also carried out as secondary outcome measurement.ResultsThirty and 34 participants concluded the study in the tocotrienols and placebo group respectively. Alpha-tocopherol levels were within the normal range for all subjects. As primary outcome, the normalisation of hepatic echogenic response was significantly higher for the tocotrienols treated group compared to the placebo group in the intention to treat analysis (P = 0.039; 95% CI = 0.896-6.488). As secondary objective, the per protocol assessment also showed significant rate of remission (P = 0.014; 95% CI = 1.117-9.456). Worsening of NAFLD grade was recorded in two patients in the placebo group, but none in the group treated with tocotrienols. No adverse events were reported for both groups.ConclusionThis is the first clinical trial that showed the hepatoprotective effects of mixed palm tocotrienols in hypercholesterolemic adults with NAFLD.Trial registrationClinicaltrials.gov, NCT00753532.

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“… Hepato-protective α-T 3 , γ-T 3 Inhibition of lipid peroxidation and oxidative damage [ 62 , 64 , 65 , 68 ] γ-T 3 , δ-T 3 Induction of the expression of CYP450, UGT1A1 nad MDR-protein 1 [ 135 , 136 ] TRF from palm oil and rice bran oil, α-T 3 , γ-T 3 , δ-T 3 Induction of hepatic antioxidant status [ 59 , 137 , 138 ] 9. Nephro-protective TRF from rice bran oil, α-T 3 , γ-T 3 Inhibition of oxidative-nitrosative stress [ 12 , 136 , 141 ] TRF from palm oil and rice bran oil, α-T 3 , γ-T 3 Downregulating the expression of NF-κB, TGF-β, TNF-α and caspase-3 [ 75 , 79 , 80 , 136 , 139 ] …”

Section: Pharmacological Propertiesmentioning

confidence: 99%

Pharmacological potential of tocotrienols: a review

et al. 2014

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Tocotrienols, members of the vitamin E family, are natural compounds found in a number of vegetable oils, wheat germ, barley, and certain types of nuts and grains. Like tocopherols, tocotrienols are also of four types viz. alpha, beta, gamma and delta. Unlike tocopherols, tocotrienols are unsaturated and possess an isoprenoid side chain. Tocopherols are lipophilic in nature and are found in association with lipoproteins, fat deposits and cellular membranes and protect the polyunsaturated fatty acids from peroxidation reactions. The unsaturated chain of tocotrienol allows an efficient penetration into tissues that have saturated fatty layers such as the brain and liver. Recent mechanistic studies indicate that other forms of vitamin E, such as γ-tocopherol, δ-tocopherol, and γ-tocotrienol, have unique antioxidant and anti-inflammatory properties that are superior to those of α-tocopherol against chronic diseases. These forms scavenge reactive nitrogen species, inhibit cyclooxygenase- and 5-lipoxygenase-catalyzed eicosanoids and suppress proinflammatory signalling, such as NF-κB and STAT. The animal and human studies show tocotrienols may be useful against inflammation-associated diseases. Many of the functions of tocotrienols are related to its antioxidant properties and its varied effects are due to it behaving as a signalling molecule. Tocotrienols exhibit biological activities that are also exhibited by tocopherols, such as neuroprotective, anti-cancer, anti-inflammatory and cholesterol lowering properties. Hence, effort has been made to compile the different functions and properties of tocotrienols in experimental model systems and humans. This article constitutes an in-depth review of the pharmacology, metabolism, toxicology and biosafety aspects of tocotrienols. Tocotrienols are detectable at appreciable levels in the plasma after supplementations. However, there is inadequate data on the plasma concentrations of tocotrienols that are sufficient to demonstrate significant physiological effect and biodistribution studies show their accumulation in vital organs of the body. Considering the wide range of benefits that tocotrienols possesses against some common human ailments and having a promising potential, the experimental analysis accounts for about a small fraction of all vitamin E research. The current state of knowledge deserves further investigation into this lesser known form of vitamin E.Electronic supplementary materialThe online version of this article (doi:10.1186/1743-7075-11-52) contains supplementary material, which is available to authorized users.

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^|^gamma;-Tocotrienol Attenuates Triglyceride through Effect on Lipogenic Gene Expressions in Mouse Hepatocellular Carcinoma Hepa 1-6

Cited by 19 publications

References 14 publications

Potential Role of Tocotrienols on Non-Communicable Diseases: A Review of Current Evidence

Potential Role of Tocotrienols on Non-Communicable Diseases: A Review of Current Evidence

Tocotrienols for normalisation of hepatic echogenic response in nonalcoholic fatty liver: a randomised placebo-controlled clinical trial

Pharmacological potential of tocotrienols: a review

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