Peroxisome proliferator–activated receptor γ down-regulation mediates the inhibitory effect of d-δ-tocotrienol on the differentiation of murine 3T3-F442A preadipocytes

Torabi, Sheida; Yeganehjoo, Hoda; Shen, Chwan Li; Mo, Huanbiao

doi:10.1016/j.nutres.2016.11.001

Cited by 12 publications

(15 citation statements)

References 38 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: 83%

“…Additionally, the anti-adipogenic activities of each T3 were reported by following the rank order of γ > δ > β > α [331,332]. The upstream molecular mechanism of anti-adipogenic activities of T3 is remains elusive, however the anti-adipogenic effect of δT3 was found to be independent of HMGCR inhibition [336].…”

Section: Comparison Between the Effects Of Tocotrienol And Tocopherolmentioning

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: 83%

Section: Comparison Between the Effects Of Tocotrienol And Tocopherolmentioning

confidence: 99%

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

et al. 2020

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“…With its strong anti-oxidative/anti-inflammatory properties, annatto-extracted TT, consisting of 90% δ -TT and 10% γ -TT, would be a good candidate to evaluate TT’s effects on T2DM-related complications, such as hyperglycemia and bone deterioration. We previously reported that δ-TT inhibited adipogenesis in 3T3-F442A preadipocytes 25 and increased fatty acid oxidation, reduced adipocyte hypertrophy, and suppressed inflammation in both liver and adipose tissue 26 . In this paper, we focused on the beneficial effect of annatto-extracted TT on glucose homeostasis and bone health in a high-fat diet (HFD)-induced T2DM model.…”

Section: Introductionmentioning

confidence: 93%

Annatto-extracted tocotrienols improve glucose homeostasis and bone properties in high-fat diet-induced type 2 diabetic mice by decreasing the inflammatory response

Shen

Kaur

Wanders

et al. 2018

Sci Rep

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Diabetes is a risk factor for osteoporosis. Annatto-extracted tocotrienols (TT) have proven benefits in preserving bone matrix. Here, we evaluated the effects of dietary TT on glucose homeostasis, bone properties, and liver pro-inflammatory mRNA expression in high-fat diet (HFD)-induced type 2 diabetic (T2DM) mice. 58 male C57BL/6 J mice were divided into 5 groups: low-fat diet (LFD), HFD, HFD + 400 mgTT/kg diet (T400), HFD + 1600 mgTT/kg diet (T1600), and HFD + 200 mg metformin/kg (Met) for 14 weeks. Relative to the HFD group, both TT-supplemented groups (1) improved glucose homeostasis by lowering the area under the curve for both glucose tolerance and insulin tolerance tests, (2) increased serum procollagen I intact N-terminal propeptide (bone formation) level, trabecular bone volume/total volume, trabecular number, connectivity density, and cortical thickness, (3) decreased collagen type 1 cross-linked C-telopeptide (bone resorption) levels, trabecular separation, and structure model index, and (4) suppressed liver mRNA levels of inflammation markers including IL-2, IL-23, IFN-γ, MCP-1, TNF-α, ITGAX and F4/80. There were no differences in glucose homeostasis and liver mRNA expression among T400, T1600, and Met. The order of osteo-protective effects was LFD ≥T1600 ≥T400 = Met >HFD. Collectively, these data suggest that TT exerts osteo-protective effects in T2DM mice by regulating glucose homeostasis and suppressing inflammation.

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“…T3 was reported to exert anti-obesity properties on several cell lines [27,28,29]. It was demonstrated to suppress adipogenesis by reducing intracellular TG and lipid droplet accumulation in mouse hepatoma Hepa 1-6 cells [30], human hepatoma HepG2 cells [20,31], 3T3-L1 preadipocytes [27,32], 3T3-F442A murine preadipocytes [23], and primary human adipose-derived stem cells (hASCs) [28,33] via oil red O staining assay. The potency of anti-adipogenic activities of T3 follows the order of γ-T3 > δ-T3 > β-T3 > α-T3 [27,28].…”

Section: Tocotrienol and Obesitymentioning

confidence: 99%

“…T3 can suppress cholesterol synthesis by inhibiting 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMGCR) post-transcriptionally, the rate-determining enzyme in the mevalonate pathway [22]. It has been shown to downregulate peroxisome proliferator-activated receptor γ (PPARγ)—the transcription factor critical in adipocytes differentiation [23]. It can prevent the activation of nuclear factor-κB (NF-κB), thereby halting tissue inflammation [24].…”

Section: Introductionmentioning

confidence: 99%

The Role of Tocotrienol in Protecting Against Metabolic Diseases

Pang¹,

Chin

2019

Molecules

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Obesity is a major risk factor for diabetes, and these two metabolic conditions cause significant healthcare burden worldwide. Chronic inflammation and increased oxidative stress due to exposure of cells to excess nutrients in obesity may trigger insulin resistance and pancreatic β-cell dysfunction. Tocotrienol, as a functional food component with anti-inflammatory, antioxidant, and cell signaling-mediating effects, may be a potential agent to complement the current management of obesity and diabetes. The review aimed to summarize the current evidence on the anti-obesity and antidiabetic effects of tocotrienol. Previous studies showed that tocotrienol could suppress adipogenesis and, subsequently, reduce body weight and fat mass in animals. This was achieved by regulating pathways of lipid metabolism and fatty acid biosynthesis. It could also reduce the expression of transcription factors regulating adipogenesis and increase apoptosis of adipocytes. In diabetic models, tocotrienol was shown to improve glucose homeostasis. Activation of peroxisome proliferator-activated receptors was suggested to be responsible for these effects. Tocotrienol also prevented multiple systemic complications due to obesity and diabetes in animal models through suppression of inflammation and oxidative stress. Several clinical trials have been conducted to validate the antidiabetic of tocotrienol, but the results were heterogeneous. There is no evidence showing the anti-obesity effects of tocotrienol in humans. Considering the limitations of the current studies, tocotrienol has the potential to be a functional food component to aid in the management of patients with obesity and diabetes.

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Peroxisome proliferator–activated receptor γ down-regulation mediates the inhibitory effect of d-δ-tocotrienol on the differentiation of murine 3T3-F442A preadipocytes

Cited by 12 publications

References 38 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

Annatto-extracted tocotrienols improve glucose homeostasis and bone properties in high-fat diet-induced type 2 diabetic mice by decreasing the inflammatory response

The Role of Tocotrienol in Protecting Against Metabolic Diseases

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