Role of dietary α- and γ-tocopherol from Rosa mosqueta oil in the prevention of alterations induced by high-fat diet in a murine model

Tapia G, Silva D, Romero N, Pettinelli P, Dossi CG, de Miguel M, González-Mañán D

Nutrition. 2018 Sep;53:1-8. doi: 10.1016/j.nut.2018.01.012. Epub 2018 Apr 3.

Abstract

OBJECTIVE:

The aim of this study was to evaluate the contribution of tocopherols present in Rosa mosqueta oil (RM) in the prevention of high-fat diet (HFD)-induced alterations.

METHODS:

Male C57 BL/6 J mice (n = 9/group) were fed for 12 wk and divided into four groups: control (CD; 10% kcal fat, 20% kcal protein, 70% kcal carbohydrates); HFD (60% as fat, 20% kcal protein, 20% kcal carbohydrates); HFD + RM (0.01 mL/g body weight/d); and HFD + RM^– without tocopherols (0.01 mL/g body weight/d). Parameters of obesity, liver steatosis (histology, triacylglycerols content), inflammation (adipose NLRP3 inflammasome, tumor necrosis factor-α and interleukin-1 β expression, hepatic nuclear factor-κB) and oxidative stress (hepatic Nrf2 activation, carbonylated proteins) were evaluated.

RESULTS:

Liver steatosis, inflammatory, and oxidative stress parameters were significantly (P < 0.05) increased in the HFD + RM^– compared with the HFD + RM, with no differences between HFD and HFD + RM^–.

CONCLUSION:

The present study suggests that α- and γ-tocopherols from RM may have an important role in the prevention of alterations induced by HFD.

Cuerq C, Henin E, Restier L, Blond E, Drai J, Marçais C, Di Filippo M, Laveille C, Michalski MC, Poinsot P, Caussy C, Sassolas A, Moulin P, Reboul E, Charriere S, Levy E, Lachaux A, Peretti N

J Lipid Res. 2018 Sep;59(9):1640-1648. doi: 10.1194/jlr.M085043. Epub 2018 Jul 18.

Abstract

Abetalipoproteinemia (ABL) and chylomicron retention disease (CMRD) are extremely rare recessive forms of hypobetalipoproteinemia characterized by intestinal lipid malabsorption and severe vitamin E deficiency. Vitamin E is often supplemented in the form of fat-soluble vitamin E acetate, but fat malabsorption considerably limits correction of the deficiency. In this crossover study, we administered two different forms of vitamin E, tocofersolan (a water-soluble derivative of RRR-α-tocopherol) and α-tocopherol acetate, to three patients with ABL and four patients with CMRD. The aims of this study were to evaluate the intestinal absorption characteristics of tocofersolan versus α-tocopherolacetate by measuring the plasma concentrations of α-tocopherol over time after a single oral load and to compare efficacy by evaluating the ability of each formulation to restore vitamin E storage after 4 months of treatment. In patients with ABL, tocofersolan and α-tocopherolacetate bioavailabilities were extremely low (2.8% and 3.1%, respectively). In contrast, bioavailabilities were higher in patients with CMRD (tocofersolan, 24.7%; α-tocopherol acetate, 11.4%). Plasma concentrations of α-tocopherol at 4 months were not significantly different by formulation type in ABL or CMRD. This study provides new insights about vitamin E status in ABL and CMRD and suggests the potential of different formulations as treatment options.

Rodriguez-Duarte J, Dapueto R, Galliussi G, Turell L, Kamaid A, Khoo NKH, Schopfer FJ, Freeman BA, Escande C, Batthyány C, Ferrer-Sueta G, López GV

Sci Rep. 2018 Aug 24;8(1):12784. doi: 10.1038/s41598-018-31218-7.

Abstract

Inflammation plays a major role in the onset and development of chronic non-communicable diseases like obesity, cardiovascular diseases and cancer. Combined, these diseases represent the most common causes of death worldwide, thus development of novel pharmacological approaches is crucial. Electrophilic nitroalkenes derived from fatty acids are formed endogenously and exert anti-inflammatory actions by the modification of proteins involved in inflammation signaling cascades. We have developed novel nitroalkenes derived from α-tocopherolaiming to increase its salutary actions by adding anti-inflammatory properties to a well-known nutraceutical. We synthesized and characterized an α-tocopherol-nitroalkene (NATOH) and two hydrosoluble analogues derived from Trolox (NATxME and NATx0). We analyzed the kinetics of the Michael addition reaction of these compounds with thiols in micellar systems aiming to understand the effect of hydrophobic partition on the reactivity of nitroalkenes. We studied NATxME in vitro showing it exerts non-conventional anti-inflammatory responses by inducing Nrf2-Keap1-dependent gene expression and inhibiting the secretion of NF-κB dependent pro-inflammatory cytokines. NATxME was also effective in vivo, inhibiting neutrophil recruitment in a zebrafish model of inflammation. This work lays the foundation for the rational design of a new therapeutic strategy for the prevention and treatment of metabolic and inflammation-related diseases.

Wong SK, Chin KY, Suhaimi FH, Ahmad F, Ima-Nirwana S

Int J Environ Res Public Health. 2018 Aug 24;15(9). pii: E1828. doi: 10.3390/ijerph15091828.

Abstract

The beneficial effects of vitamin E in improving components of MetS or bone loss have been established. This study aimed to investigate the potential of palm vitamin E (PVE) as a single agent, targeting MetS and bone loss concurrently, using a MetS animal model. Twelve-week-old male Wistar rats were divided into five groups. The baseline group was sacrificed upon arrival. The normal group was given standard rat chow. The remaining three groups were fed with high-carbohydrate high-fat (HCHF) diet and treated with tocopherol-stripped corn oil (vehicle), 60 mg/kg or 100 mg/kg PVE. At the end of the study, the rats were evaluated for MetS parameters and bone density. After euthanasia, blood and femurs were harvested for the evaluation of lipid profile, bone histomorphometric analysis, and remodeling markers. PVE improved blood pressure, glycemic status, and lipid profile; increased osteoblast surface, osteoid surface, bone volume, and trabecular thickness, as well as decreased eroded surface and single-labeled surface. Administration of PVE also significantly reduced leptin level in the HCHF rats. PVE is a potential agent in concurrently preventing MetS and protecting bone loss. This may be, in part, achieved by reducing the leptin level and modulating the bone remodeling activity in male rats.

Montagnani Marelli M, Marzagalli M, Fontana F, Raimondi M, Moretti RM, Limonta P

J Cell Physiol. 2018 Aug 1. doi: 10.1002/jcp.27075. [Epub ahead of print]

Abstract

Vitamin E is composed of two groups of compounds: α-, β-, γ-, and δ-tocopherols (TPs), and the corresponding unsaturated tocotrienols(TTs). TTs are found in natural sources such as red palm oil, annatto seeds, and rice bran. In the last decades, TTs (specifically, γ-TT and δ-TT) have gained interest due to their health benefits in chronic diseases, based on their antioxidant, neuroprotective, cholesterol-lowering, anti-inflammatory activities. Several in vitro and in vivo studies pointed out that TTs also exert a significant antitumor activity in a wide range of cancer cells. Specifically, TTs were shown to exert antiproliferative/proapoptotic effects and to reduce the metastatic or angiogenic properties of different cancer cells; moreover, these compounds were reported to specifically target the subpopulation of cancer stem cells, known to be deeply involved in the development of resistance to standard therapies. Interestingly, recent studies pointed out that TTs exert a synergistic antitumor effect on cancer cells when given in combination with either standard antitumor agents (i.e., chemotherapeutics, statins, “targeted” therapies) or natural compounds with anticancer activity (i.e., sesamin, epigallocatechin gallate (EGCG), resveratrol, ferulic acid). Based on these observations, different TT synthetic derivatives and formulations were recently developed and demonstrated to improve TT water solubility and to reduce TT metabolism in cancer cells, thus increasing their biological activity. These promising results, together with the safety of TT administration in healthy subjects, suggest that these compounds might represent a new chemopreventive or anticancer treatment (i.e., in combination with standard therapies) strategy. Clinical trials aimed at confirming this antitumor activity of TTs are needed.

Hamułka J, Górnicka M, Sulich A, Frąckiewicz J

Clin Nutr. 2018 Jul 20. pii: S0261-5614(18)31213-5. doi: 10.1016/j.clnu.2018.07.011. [Epub ahead of print]

Abstract

BACKGROUND & AIMS:

Studies on changes in plasma α-tocopherol levels during body fat reduction in obese persons are not clear. The aim of the present study was to assess factors associated with α-tocopherol status in obese people and to examine changes in α-tocopherolstatus after a 6-week AntioxObesity weight loss program.

METHODS:

The study was conducted in 60 overweight or obese adults, aged 18-54 years old. Food intake data were collected using the 3-day record method and a semi-quantitative food-frequency questionnaire. Anthropometric measurements included: height (H), body weight, waist circumference (WC) and hip circumference (HC), body composition: fat mass (FM) and fat-free mass (FFM), subcutaneous fat (SF) and visceral fat (VF). Lipid profile, α-tocopherol concentration, glutathione peroxidase (GPx) activity, total antioxidant capacity (TAC) in plasma and superoxide dismutase (SOD) activity in erythrocytes were determined.

RESULTS:

Energy, fat, and carbohydrate intakes decreased significantly in all subjects (P < 0.001). Body weight, WC, body mass index (BMI), waist-to height ratio (WHtR), and FM, VF and SF decreased significantly during the 6 weeks in all subjects. Plasma α-tocopherolsignificantly decreased during the program (P = 0.006). No changes were observed for SOD activity, but GPx activity and TAC decreased significantly (P = 0.001; P = 0,023, respectively). Plasma α-tocopherol concentration after 6 weeks of the AntioxObesity program was strongly associated with baseline plasma α-tocopherol, changes in TC, VF and FM. Low α-tocopherol status (<20 μmol/L) was found in 78% of the women and 68% of the men, after 6 weeks of the AntioxObesity program. Men were characterized by a greater decrease in weight, BMI, WC, FM, VF, SF and TAC compared to women.

CONCLUSIONS:

A 6-week weight loss program lowered α-tocopherol status in overweight and obese people. Low baseline α-tocopherolstatus and adiposity in obese adults negatively affected α-tocopherol status after 6 weeks weight loss program. These results, coupled with excessive weight and low α-tocopherol intake, led to the finding that there was an increased risk of oxidative stress diseases in adults on a reduced diet. Long-term dietary restriction program for obese patients should be monitored to avoid α-tocopherol deficiency, and take into account higher dietary α-tocopherol requirements for obese people.

Wong SK, Chin KY, Suhaimi FH, Ahmad F, Ima-Nirwana S

Bone. 2018 Jul 7. pii: S8756-3282(18)30260-6. doi: 10.1016/j.bone.2018.07.003. [Epub ahead of print]

Abstract

Metabolic syndrome (MetS) is associated with osteoporosis due to the underlying inflammatory and hormonal changes. Annatto tocotrienolhas been shown to improve medical complications associated with MetS or bone loss in animal studies. This study aimed to investigate the effects of annatto tocotrienol as a single treatment for MetS and osteoporosis in high-carbohydrate high-fat (HCHF) diet-induced MetS animals. Three-month-old male Wistar rats were randomly divided into five groups. The baseline group was euthanized at the onset of the study. The normal group received standard rat chow and tap water. The remaining groups received HCHF diet and treated with three different regimens orally daily: (a) tocopherol-stripped corn oil (the vehicle of tocotrienol), (b) 60 mg/kg annatto tocotrienol, and (c) 100 mg/kg annatto tocotrienol. At the end of the study, measurements of MetS parameters, body compositions, and bone mineral density were performed in animals before sacrifice. Upon euthanasia, blood and femur of the rats were harvested for the evaluations of bone microstructure, biomechanical strength, remodelling activities, hormonal changes, and inflammatory response. Treatment with annatto tocotrienol improved all MetS parameters (except abdominal obesity), trabecular bone microstructure, bone strength, increased osteoclast number, normalized hormonal changes and inflammatory response in the HCHF animals. In conclusion, annatto tocotrienol is a potential agent for managing MetS and osteoporosis concurrently. The beneficial effects of annatto tocotrienol may be attributed to its ability to prevent the hormonal changes and pro-inflammatory state in animals with MetS.

Campos-Perez W, Torres-Castillo N, Perez-Robles M, Muñoz-Valle JF, Vizmanos-Lamotte B, Martinez-Lopez E

J Nutrigenet Nutrigenomics. 2018 Feb 2;10(5-6):172-180. doi: 10.1159/000486160. [Epub ahead of print]

Abstract

BACKGROUND/AIM:

One of the beneficial effects associated with vitamin E intake is the enhancement of peroxisome proliferator-activated receptor gamma (PPARγ) activity and the consequent upregulation of adiponectin expression. The aim of this study was to analyze the adiponectin levels in subjects with the Pro12Ala polymorphism of PPARG according to vitamin E intake.

METHODS:

A total of 283 subjects were enrolled. Total vitamin E intake was estimated based on a validated 3-day food consumption record and analyzed using Nutritionist ProTM software. The Pro12Ala polymorphism (rs1801282) was determined by allelic discrimination. The adiponectin levels were measured by an ELISA assay.

RESULTS:

Vitamin E intake was deficient in all subjects (1.50 ± 1.78 mg/day). Subjects with higher vitamin E intake levels and the Pro12Ala/Ala12Ala genotype had statistically significant higher levels of serum adiponectin than subjects with the Pro12Pro genotype (4.4 [3.2-5.7] vs. 2.7 [2.0-3.5] μg/mL; p = 0.024).

CONCLUSIONS:

Our results suggest that increased consumption of vitamin E should be encouraged since it has been reported that vitamin E promotes adiponectin expression via PPARγ activation. Subjects with Pro12Pro genotype had lower serum adiponectin levels than subjects with Pro12Ala/Ala12Ala genotype; therefore, they might be at higher risk of developing metabolic complications.

Rios R, Raya AI, Pineda C, Rodriguez M, Lopez I, Aguilera-Tejero E

BMC Nephrol. 2017 Dec 28;18(1):374. doi: 10.1186/s12882-017-0790-4.

Abstract

BACKGROUND:

High fat diets are implicated in the pathogenesis of metabolic syndrome, obesity and renal disease. Previous studies have revealed that high fat diets promote vascular calcification in uremic rats. Moreover, vitamin E has been shown to prevent uremic calcifications in genetically obese Zucker rats fed standard diet. The objective of this study was to investigate the influence of vitamin E supplementation on the development of extraskeletal calcifications in non-obese (wild type) uremic rats fed high fat diets.

METHODS:

Wistar rats (n = 32) were preconditioned by feeding either a normal (NF) or high fat (HF) diet for 45 days and subsequently were subjected to 5/6 nephrectomy (Nx). Just before performing the first Nx step, a blood sample (Pre-Nx) was obtained. After Nx rats were switched to a diet with 0.9% phosphorus and supplemented with calcitriol. Also, after Nx, half of the rats from each group (NF and HF) were treated with vitamin E (VitE) in the diet (30,000 mg/kg) and the other half were maintained on basic VitE requirements (27 mg/kg). Thus, rats were allotted to four experimental groups: Nx-NF (n = 8), Nx-NF-VitE (n = 8), Nx-HF (n = 8) and Nx-HF-VitE (n = 8). At the time of sacrifice (day 66), blood and tissue samples were obtained.

RESULTS:

Feeding a HF diet for 45 days did not increase body weight but elicited hyperglycemia, hypertriglyceridemia, an increase in plasma fibroblast growth factor 23 and a reduction in plasma calcitriol concentrations. After Nx, rats fed HF diet showed substantial extraskeletal calcification with aortic calcium content that was higher than in rats fed NF diet. Supplementation with VitE significantly (p < 0.05) reduced aortic (from 38.4 ± 8.8 to 16.5 ± 1.4 mg/g), gastric (from 5.6 ± 2.7 to 1.2 ± 0.4 mg/g) and pulmonary (from 1.8 ± 0.3 to 0.3 ± 0.2 mg/g) calcium content in rats on HF diets.

CONCLUSIONS:

Uremic rats fed HF diets developed more severe extraosseous calcifications than their normocaloric-fed counterparts and dietary VitE supplementation protected against uremic calcifications in rats fed HF diets. Thus, eating energy-rich foods should be discouraged in patients with renal disease and their deleterious effect may be ameliorated with adequate antioxidant supply.

Waniek S, di Giuseppe R, Plachta-Danielzik S, Ratjen I, Jacobs G, Koch M, Borggrefe J, Both M, Müller HP, Kassubek J, Nöthlings U, Esatbeyoglu T, Schlesinger S, Rimbach G, Lieb W

Nutrients. 2017 Oct 18;9(10). pii: E1143. doi: 10.3390/nu9101143.

Abstract

We aimed to relate circulating α- and γ-tocopherol levels to a broad spectrum of adiposityrelated traits in a cross-sectional Northern German study. Anthropometric measures were obtained, and adipose tissue volumes and liver fat were quantified by magnetic resonance imaging in 641 individuals (mean age 61 years; 40.6% women). Concentrations of α- and γ-tocopherol were measured using high performance liquid chromatography. Multivariable-adjusted linear and logistic regression were used to assess associations of circulating α- and γ-tocopherol/cholesterol ratio levels with visceral (VAT) and subcutaneous adipose tissue (SAT), liver signal intensity (LSI), fatty liver disease (FLD), metabolic syndrome (MetS), and its individual components. The α- tocopherol/cholesterol ratio was positively associated with VAT (β scaled by interquartile range (IQR): 0.036; 95%Confidence Interval (CI): 0.0003; 0.071) and MetS (Odds Ratio (OR): 1.83; 95% CI: 1.21-2.76 for 3rd vs. 1st tertile), and the γ-tocopherol/cholesterol ratio was positively associated with VAT (β scaled by IQR: 0.066; 95% CI: 0.027; 0.104), SAT (β scaled by IQR: 0.048; 95% CI: 0.010; 0.087) and MetS (OR: 1.87; 95% CI: 1.23-2.84 for 3rd vs. 1st tertile). α- and γ-tocopherol levels were positively associated with high triglycerides and low high density lipoprotein cholesterol levels (all Ptrend < 0.05). No association of α- and γ-tocopherol/cholesterol ratio with LSI/FLD was observed. Circulating vitamin E levels displayed strong associations with VAT and MetS. These observations lay the ground for further investigation in longitudinal studies.