Nutrient pattern of unsaturated fatty acids and vitamin E increase resting metabolic rate of overweight and obese women

Habib Yarizadeh, Leila Setayesh, Caroline Roberts, Mir Saeed Yekaninejad, Khadijeh Mirzaei

Int J Vitam Nutr Res . 2020 Jul 16;1-9. doi: 10.1024/0300-9831/a000664. Online ahead of print.


Objectives: Obesity plays an important role in the development of chronic diseases including cardiovascular disease and diabetes. A low resting metabolic rate (RMR) for a given body size and composition is a risk factor for obesity, however, there is limited evidence available regarding the association of nutrient patterns and RMR. The aim of this study was to determine the association of nutrient patterns and RMR in overweight and obese women. Study design: This cross-sectional study was conducted on 360 women who were overweight or obese. Method: Dietary intake was assessed using a semi-quantitative standard food frequency questionnaire (FFQ). Nutrient patterns were also extracted by principal components analysis (PCA). All participants were evaluated for their body composition, RMR, and blood parameters. Result: Three nutrient patterns explaining 64% of the variance in dietary nutrients consumption were identified as B-complex-mineral, antioxidant, and unsaturated fatty acid and vitamin E (USFA-vit E) respectively. Participants were categorized into two groups based on the nutrient patterns. High scores of USFA-vit E pattern was significantly associated with the increase of RMR (β = 0.13, 95% CI = 0.79 to 68.16, p = 0.04). No significant associations were found among B-complex-mineral pattern (β = -0.00, 95% CI = -49.67 to 46.03, p = 0.94) and antioxidant pattern (β = 0.03, 95% CI -41.42 to 22.59, p = 0.56) with RMR. Conclusion: Our results suggested that the “USFA-vit E” pattern (such as PUFA, oleic, linoleic, vit.E, α-tocopherol and EPA) was associated with increased RMR.

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Tocotrienols Influence Body Weight Gain and Brain Protein Expression in Long-Term High-Fat Diet-Treated Mice

Yugo Kato, Yoshinori Aoki, Koji Fukui

Int J Mol Sci . 2020 Jun 25;21(12):4533. doi: 10.3390/ijms21124533.


Obesity induces serious diseases such as diabetes and cardiovascular disease. It has been reported that obesity increases the risk of cognitive dysfunction. Cognitive dysfunction is a characteristic symptom of Alzheimer’s and Parkinson’s diseases. However, the detailed mechanisms of obesity-induced cognitive dysfunction have not yet been elucidated. The onset and progression of obesity-induced severe secondary diseases such as diabetes, cardiovascular events, and hypertension are deeply connected to oxidative stress. We hypothesized that obesity induces cognitive dysfunction via acceleration of reactive oxygen species (ROS) production. Vitamin E, which is a lipophilic vitamin, has strong antioxidative effects and consists of two groups: tocopherols and tocotrienols. Recently, it has been demonstrated that tocotrienols have strong neuroprotective and anti-obesity effects. In this study, we fed mice a high-fat diet (HFD) from 9 to 14 months of age and assessed the effect of tocotrienols treatment on body weight, brain oxidation levels, and cognitive function. The results revealed that treatment with tocotrienols inhibited body weight gain; further, tocotrienols reached the brain and attenuated oxidation in HFD-treated mice. These results indicate that tocotrienols have anti-obesity effects and inhibit obesity-induced brain oxidation.

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Relationship Between Serum Vitamin E Concentration in First Trimester and the Risk of Developing Hypertension Disorders Complicating Pregnancy

W Y Meng, W T Huang, J Zhang, M Y Jiao, L Jin, L Jin

Beijing Da Xue Xue Bao Yi Xue Ban . 2020 Jun 18;52(3):470-478.


Objective: To investigate the incidence of hypertension disorders complicating pregnancy (HDCP) and vitamin E (VE) nutritional status among pregnant women in Beijing, and to determine the relationship between serum VE concentration in the first trimester of pregnancy and the risk of developing HDCP.

Methods: A retrospective cohort study was performed including 22 283 cases of pregnant women who underwent singleton deliveries in Tongzhou Maternal & Child Health Hospital of Beijing from January 2016 through December 2018 and received tests of serum VE concentrations in the first trimester of pregnancy. Nonconditional Logistic regression model was used to analyze the association between serum VE concentration levels and the risk of developing HDCP.

Results: The total incidence of HDCP was 5.4%, with the incidence of gestational hypertension around 2.1% and the incidence of preeclampsia-eclampsia around 3.3%. The median concentration of serum VE in early pregnancy was 10.1 (8.8-11.6) mg/L, and 99.7% of the participants had normal serum VE concentrations. The incidence of gestational hypertension and that of preeclampsia-eclampsia had been annually increasing in three years; a linear-by-linear association had also been observed between the serum VE concentrations and the years of delivery. According to the results of the univariable and the multivariable Logistic regression analyses, higher risks of developing HDCP had been observed among women with higher serum VE concentrations. Compared to those with serum VE concentrations in interquartile range (P25P75) of all the participants, the women whose serum VE concentrations above P75 were at higher risks to be attacked by HDCP (OR = 1.34, P < 0.001), gestational hypertension (OR = 1.39, P = 0.002), or preeclampsia-eclampsia (OR = 1.34, P = 0.001), as suggested by the results of the multivariable Logistic regression model analyses. In addition, the women with serum VE concentrations of 11.2 mg/L or above had a significantly higher risk of developing HDCP than those whose serum VE concentrations of P40P60 of all the participants, and this risk grew higher as serum VE concentrations in the first trimester of pregnancy increased.

Conclusion: Women in Beijing are at good nutritional status. From January 2016 to December 2018, the incidence of HDCP increased with serum VE concentration level, and serum VE concentration of 11.2 mg/L is an indicator of an increased risk of developing HDCP, suggesting that pregnant women should take nutritional supplements containing VE carefully.

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Effects of Royal Jelly and Tocotrienol Rich Fraction in Obesity Treatment of Calorie-Restricted Obese Rats: A Focus on White Fat Browning Properties and Thermogenic Capacity

Naimeh Mesri Alamdari, Pardis Irandoost, Neda Roshanravan, Mohammadreza Vafa, Mohammad Asghari Jafarabadi, Shahriar Alipour, Leila Roshangar, Mohammadreza Alivand, Farnaz Farsi, Farzad Shidfar

Nutr Metab (Lond) . 2020 Jun 1;17:42. doi: 10.1186/s12986-020-00458-8. eCollection 2020.


Background: Obesity has reached an alarming rate worldwide. Promoting thermogenesis via increasing the function of brown adipose tissue (BAT) or white adipose tissue (WAT) browning has been proposed as a new protective approach against obesity. The goal of this study was to evaluate the effects of Royal Jelly (RJ) and tocotrienol rich fraction (TRF) on BAT activation and WAT browning during calorie restriction diet (CRD) in obesity model.

Methods: In this experimental study, 50 obese Wistar rats were randomly divided into 5 groups and then received one of the following treatments for a period of 8-week: High-fat diet (HFD), CRD, RJ + CRD, TRF + CRD, and RJ + TRF + CRD. Effects of RJ and TRF, individually and in combination on body weight and the expression of key thermoregulatory genes in WAT and BAT were examined by quantitative real-time (qRT-PCR). Also, morphological alterations were assessed by hematoxylin and eosin staining.

Results: RJ (- 67.21 g ±4.84 g) and RJ + TRF (- 73.29 g ±4.51 g) significantly reduced weight gain relative to the CRD group (- 40.70 g ±6.50 g, P < 0.001). In comparison with the CRD group, RJ and RJ + TRF remarkably enhanced the uncoupling protein1 (UCP1) expression in WAT (5.81, 4.72 fold, P < 0.001) and BAT (4.99, 4.75 fold, P < 0.001). The expression of PR domain containing 16(PRDM 16), cAMP response element-binding protein1 (CREB1), P38 mitogen-activated protein kinases (P38MAPK), and Bone morphogenetic protein8B (BMP8B) have significantly increased following RJ and RJ + TRF treatments (P < 0.001). However, the expression levels of CCAAT/enhancer-binding protein beta (CEBPβ) and Bone morphogenetic protein7 ( BMP7) did not remarkably change. Multilocular beige cells in WAT and compacted dense adipocytes were also observed in BAT of RJ and RJ + TRF received groups. TRF showed no substantial effects on the expression of the mentioned thermoregulatory genes and brown fat-like phenotype.

Conclusion: Our results suggest that, Royal Jelly promotes thermogenesis and browning of WAT, contributing to an increase in energy expenditure. Thus, Royal Jelly may give rise to a novel dietary choice to attenuate obesity.

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Metabolic Benefits of Annatto-Extracted Tocotrienol on Glucose Homeostasis, Inflammation, and Gut Microbiome

Eunhee Chung, Moamen M Elmassry, Pratibha Kottapalli, Kameswara Rao Kottapalli, Gurvinder Kaur, Jannette M Dufour, Kandis Wright, Latha Ramalingam, Naima Moustaid-Moussa, Rui Wang, Abdul N Hamood, Chwan-Li Shen

Nutr Res . 2020 May;77:97-107. doi: 10.1016/j.nutres.2020.04.001. Epub 2020 Apr 17.


Emerging evidence suggests that the gut microbiome plays an important role in the pathophysiology of both obesity and type 2 diabetes mellitus. We previously reported that dietary annatto-extracted tocotrienol exerts beneficial effects by modulating inflammatory responses in mice fed a high-fat diet (HFD). The purpose of this study was to test the hypothesis that tocotrienol supplementation when combined with an HFD would result in an altered gut microbiota composition. For 14 weeks, forty-eight male C57BL/6J mice were assigned to 4 groups-low-fat diet, HFD, HFD supplemented with annatto-extracted tocotrienol at 800 mg/kg diet (AT), and HFD supplemented with metformin at 200 mg/kg diet. Glucose homeostasis was assessed by glucose and insulin tolerance tests, serum and pancreas insulin levels, and histological assessments of insulin and glucagon in pancreatic tissue. The concentrations of adipokines were measured in white adipose tissues. For the gut microbiome analysis, cecal content was collected, DNA was extracted, and 16S rRNA gene sequencing was performed. AT supplementation improved glucose homeostasis and lowered resistin, leptin, and interleukin-6 levels in white adipose tissue. Relative to the HFD group, AT-supplemented mice showed a decrease in the Firmicutes to Bacteroidetes ratio and had a lower abundance of Ruminococcus lactaris, Dorea longicatena, and Lachnospiraceae family. The relative abundance of Akkermansia muciniphila was increased in the AT group compared to the low-fat diet group. The association between the metabolic improvements and the identified bacterial taxa suggests a potential metabolic modulation caused by AT supplementation through the gut microbiota composition in mice fed an HFD.

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Effect of High Fructose-Induced Metabolic Syndrome on Tissue Vitamin E and Lipid Peroxide Levels in Rats

Akira Kitagawa, Yoshiji Ohta, Koji Ohashi, Koji Yashiro, Kenji Fukuzawa

J Nutr Sci Vitaminol (Tokyo) . 2020;66(2):200-206. doi: 10.3177/jnsv.66.200.


In the present study, we examined the effect of high fructose-induced metabolic syndrome (MetS) on tissue vitamin E and lipid peroxide (LPO) levels in rats. Feeding of a diet containing 60% fructose (HFD) to Wistar rats for 2, 4, and 6 wk caused week-dependent increases in HOMA-IR score and serum insulin, triglyceride, total cholesterol, and free fatty acid concentrations. Each week HFD feeding increased serum vitamin E concentration. Six-week HFD feeding reduced vitamin E status (the serum ratio of vitamin E/triglyceride+total cholesterol). Four- and 6-wk HFD feeding increased serum LPO concentration. Two-week HFD feeding increased liver, heart, kidney, and skeletal muscle (SM) vitamin E contents and decreased white adipose tissue (WAT) vitamin E content. Four- and 6-wk HFD feeding further reduced WAT vitamin E content without affecting the increased kidney and SM vitamin E contents. Six-week HFD feeding reduced the increased liver and heart vitamin E contents below the level of non-HFD feeding. Four-week HFD feeding increased heart and WAT LPO contents. Six-week HFD feeding increased liver LPO content and further increased heart and WAT LPO contents. Kidney and SM LPO contents remained unchanged. These results indicate that HFD-rats with early MetS have increased liver, kidney, heart, and SM vitamin E contents and decreased WAT vitamin E content under unchanged tissue LPO content and vitamin E status, while HFD-fed rats with progressed MetS have both decreased liver, heart, and WAT vitamin E contents under increased tissue LPO content and disrupted vitamin E status.

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Alterations of Serum Vitamin E and Vitamin A Concentrations of Ponies and Horses During Experimentally Induced Obesity

Carola Schedlbauer, Dominique Blaue, Jens Raila, Ingrid Vervuert

J Anim Physiol Anim Nutr (Berl) . 2020 May 14. doi: 10.1111/jpn.13385. Online ahead of print.


Vitamin A, vitamin E and retinol-binding protein 4 (RBP4) are a focus of current obesity research in humans. The impact of body weight (BW) gain on fat-soluble vitamins and its associated parameters in equines has not been previously reported. Ten Shetland ponies and 9 Warmblood horses, all adult geldings, non-obese and healthy, were fed an excessive energy diet for 20 months to induce BW gain. Serum α-tocopherol (vitamin E), retinol (vitamin A), retinol-binding protein 4 (RBP4) and retinol/RBP4 ratio were analysed before BW gain induction and at six timepoints during the BW gaining period. The mean (±SD) % BW gain achieved during two years of excess energy intake was 29.9 ± 19.4% for ponies and 17 ± 6.74% for horses. Serum α-tocopherol increased significantly in ponies and horses during excess energy intake and circulating α-tocopherol levels correlated positively with α-tocopherol intake (r = .6; p < .001). Serum retinol concentrations showed variations during the study but without relation to intake. Serum RBP4 decreased at the end of the study. The retinol/RBP4 ratio increased with BW gain without differences between ponies and horses. In comparison with human research, the increase in the retinol/RBP4 ratio was unexpected and needs further elucidation.

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High-throughput Profiling Reveals Perturbation of Endoplasmic Reticulum Stress-Related Genes in Atherosclerosis Induced by High-Cholesterol Diet and the Protective Role of Vitamin E

Perinur Bozaykut, Ruchan Ekren, Osman Ugur Sezerman, Vadim N Gladyshev, Nesrin Kartal Ozer

Biofactors . 2020 May 8. doi: 10.1002/biof.1635.


Formation of atherosclerotic plaques, called atherogenesis, is a complex process affected by genetic and environmental factors. It was proposed that endoplasmic reticulum (ER) stress is an important factor in the pathogenesis of atherosclerosis and that vitamin E affects atherosclerotic plaque formation via its antioxidant properties. Here, we investigated ER stress-related molecular mechanisms in high-cholesterol diet (HCD, 2%)-induced atherosclerosis model and the role of vitamin E supplementation in it, beyond its antioxidant properties. The consequences of HCD and vitamin E supplementation were examined by determining protein levels of ER stress markers in aortic tissues. As vitamin E supplementation acts on several unfolded protein response (UPR) factors, it decreased ER stress induced by HCD. To elucidate the associated pathways, gene expression profiling was performed, revealing differentially expressed genes enriched in ER stress-related pathways such as the proteasome and the apoptosis pathways. We further assessed the proteasomal activity impaired by HCD in the aorta and showed that vitamin E reversed it to that of control animals. Overall, the study characterized the effects of HCD and vitamin E on ER stress-related gene expression, revealing the role of proteolytic systems during atherogenesis.

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Cholesterol induced autophagy via IRE1/JNK pathway promotes autophagic cell death in heart tissue

Sozen E, Yazgan B, Tok OE, Demirel T, Ercan F, Proto JD, Ozer NK

Metabolism. 2020 Mar 14;106:154205. doi: 10.1016/j.metabol.2020.154205. [Epub ahead of print]



Cardiovascular diseases (CVDs), with highest mortality and morbidity rates, are the major cause of death in the world. Due to the limited information on heart tissue changes, mediated by hypercholesterolemia, we planned to investigate molecular mechanisms of endoplasmic reticulum (ER) stress and related cell death in high cholesterol fed rabbit model and possible beneficial effects of α-tocopherol.


Molecular changes in rabbit heart tissue and cultured cardiomyocytes (H9c2 cells) were measured by western blotting, qRT-PCR, immunflouresence and flow cytometry experiments. Histological modifications were assessed by light and electron microscopes, while degradation of mitochondria was quantified through confocal microscope.


Feeding rabbits 2% cholesterol diet for 8 weeks and treatment of cultured cardiomyocytes with 10 μg/mL cholesterol for 3 h induced excessive autophagic activity via IRE1/JNK pathway. While no change in ER-associated degradation (ERAD) and apoptotic cell death were determined, electron and confocal microscopy analyses in cholesterol supplemented rabbits revealed significant parameters of autophagic cell death, including cytoplasmic autophagosomes, autolysosomes and organelle loss in juxtanuclear area as well as mitochondria engulfment by autophagosome. Either inhibition of ER stress or JNK in cultured cardiomyocytes or α-tocopherol supplementation in rabbits could counteract the effects of cholesterol.


Our findings underline the essential role of hypercholesterolemia in stimulating IRE1/JNK branch of ER stress response which then leads to autophagic cell death in heart tissue. Results also showed α-tocopherol as a promising regulator of autophagic cell death in cardiomyocytes.

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Actions of annatto-extracted tocotrienol supplementation on obese postmenopausal women: study protocol for a double-blinded, placebo-controlled, randomised trial

Aryaie A, Tinsley G, Lee J, Watkins BA, Moore L, Alhaj-Saleh A, Shankar K, Wood SR, Wang R, Shen CL

BMJ Open. 2020 Mar 8;10(3):e034338. doi: 10.1136/bmjopen-2019-034338.



Obesity is a major health concern in postmenopausal women, and chronic low-grade inflammation contributes to the development of obesity. Cellular studies and high-fat-diet-induced obese mouse model mimicking obesity show the antiobesity effect of annatto-extracted tocotrienols (TT) with antioxidant capability. We aim to assess the safety and efficacy of TT consumption for lipid-related parameters in obese postmenopausal women.


Eligible obese postmenopausal women will be randomly assigned to placebo group (430 mg olive oil) and TT group (DeltaGold Tocotrienol 70%) for 24 weeks. In the present study, the primary outcome is total/regional fat mass and visceral adipose tissue. The secondary outcomes include lipid profile in serum, mRNA expression of fatty acid synthase and carnitine palmitoyltransferase 1A in fat tissue, oxylipins and endocannabinoids in plasma and adipose tissue, abundance and composition of intestinal microbiome in faeces, high-sensitivity C-reactive protein (hs-CRP) in serum and leptin in serum. Every participant will be evaluated at 0 (prior to starting intervention) and 24 weeks of intervention, except for serum lipid profile and hs-CRP at 0, 12 and 24 weeks. ‘Intent-to-treat‘ principle is employed for data analysis. Hierarchical linear modelling is used to estimate the effects of dietary TT supplementation while properly accounting for dependency of data and identified covariates. To our knowledge, this is the first randomised, placebo-controlled, double-blinded study to determine dietary TT supplementation on an obese population. If successful, this study will guide the future efficacy TT interventions and TT can be implemented as an alternative for obese population in antiobesity management.


This study has been approved by the Bioethics Committee of the Texas Tech University Health Sciences Center, Lubbock. An informed consent form will be signed by a participant before enrolling in the study. The results from this trial will be actively disseminated through academic conference presentation and peer-reviewed journals.

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