Vitamin A and its derivatives have been shown to modulate the immune system via retinoic acid receptor (RAR). This study explored the impact of retinyl palmitate supplementation on RAR subtype gene expression in peripheral blood mononuclear cells (PBMCs) in multiple sclerosis (MS) patients. The study designed as a double-blind randomized clinical trial in which relapsing remitting multiple sclerosis patients were evaluated. Both groups received one capsule 50,000 IU vitamin D3 per 2 weeks and one intramuscular injection interferon beta-1a per week. The intervention group received one 25,000 IU retinyl palmitate capsule daily for 6 months and the placebo group received one placebo capsule daily. The PBMCs were isolated from participants and the expression level changes of RAR-α and RAR-γ genes were determined by real-time PCR. After supplementation, in the intervention group, the RAR-α gene expression level was significantly decreased compared to the placebo group (p = 0.03); however, the expression of RAR-γ gene did not significantly change (p = 0.10). These results show that vitamin A supplementation can significantly downregulate the expression of RAR-α gene in PBMCs of MS patients that suggest the presence of in vivo regulatory mechanisms for the action of vitamin A on the immune system.

Diabetes mellitus is one of the most wide spread endocrine disorders and an important developing health problem in the world. Cardiovascular disease is a common complication of type 2 diabetes. Several risk factors for coronary heart disease cosegregate in type 2 diabetes, including hyperglycemia, hyperlipaemia, increases production of free radical and decrease in antioxidant defense system. In this study we evaluated the effect of vitamin C supplementation on fasting and postprandial oxidative stress and lipid profile in type 2 diabetic patients. 30 patients with type 2 diabetes from Nader Kazemi Clinic, Shiraz, Iran were randomly divided into 2 groups; vitamin C treatment group (1000 mg d(-1)) and placebo group from May to September 2010. Fasting and postprandial lipid profile and Malondialdehyde (MDA) level were measured at the beginning of the study and after six weeks of supplementation. Data analysis was carried out using Mann-Whitney U test with p < 0.05 being significant by SPSS software version 16.The result of the study showed a significantly decrease in fasting (p = 0.006) and postprandial MDA (p < 0.001) in vitamin C group compare to placebo group but not in lipid profile. This study suggests that vitamin C supplementation can decrease fasting and postprandial oxidative stress and may prevent diabetes complication.

n-3 highly unsaturated fatty acids (n-3 HUFA) directly and indirectly regulate lipid metabolism, energy balance and the inflammatory response. We investigated changes to the n-3 HUFA score of healthy adults, induced by different types and amounts of conjugated linoleic acid (CLA)-enriched (ENCH) cheeses consumed for different periods of time, compared to dietary fish oil (FO) pills (500 mg, each containing 100 mg of eicosapentaenoic and docosahexaenoic acids—EPA+DHA) or α-linolenic acid (ALA)-rich linseed oil (4 g, containing 2 g of ALA). A significant increase in the n-3 HUFA score was observed, in a dose-dependent manner, after administration of the FO supplement. In terms of the impact on the n-3 HUFA score, the intake of ENCH cheese (90 g/day) for two or four weeks was equivalent to the administration of one or two FO pills, respectively. Conversely, the linseed oil intake did not significantly impact the n-3 HUFA score. Feeding ENCH cheeses from different sources (bovine, ovine and caprine) for two months improved the n-3 HUFA score by increasing plasma DHA, and the effect was proportional to the CLA content in the cheese. We suggest that the improved n-3 HUFA score resulting from ENCH cheese intake may be attributed to increased peroxisome proliferator-activated receptor alpha (PPAR-α) activity. This study demonstrates that natural ENCH cheese is an alternative nutritional source of n-3 HUFA in humans.

Background/Aims: We studied peroxisome proliferator-activated receptor-γ coactivator-1α (PPARGC1A) gene variations at the 23815227–23815706 positions and examined their possible correlation with obesity-related conditions and resting energy expenditure (REE). We investigated the expression of PPARGC1A, mitogen-activated protein kinase (MAPK) and uncoupling protein 2 (UCP2), which play key roles in cellular energy expenditure, in a cellular model consisting of peripheral blood mononuclear cells, and compared them with various genotypes of the PPARGC1A gene. Methods: In total, 100 normal-weight and 129 obese subjects participated in the current study. All subjects were assessed for REE and body composition. We sequenced the PPARGC1A gene. Real-time PCR was used for determining the PPARGC1A, MAPK, and UCP2 gene expression. Results: There were significant differences in terms of body mass index, fat mass, low-density lipoprotein, insulin levels, REE/kg body weight, and REE/lean body mass among rs17574213 genotypes. There were significant differences in total cholesterol and low-density lipoprotein cholesterol levels among the various genotypes of Gly482Ser (rs8192678) and rs3755863. The relative PPARGC1A, MAPK, and UCP2 gene expressions had similar trends in the two studied SNPs, and the expression level of these genes was lowest in the TT genotype of Gly482Ser and rs3755863 and highest in the CC genotype of Gly482Ser and rs3755863. Conclusions: Our findings suggest that PPARGC1A variations may influence PPARGC1A expression and the coordinating regulators of downstream targets in energy homeostasis. Further study is needed to shed some light on this process.

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To evaluate whether a peculiar plasma profile of fatty acids and endocannabinoidome (eCBome)-related mediators may be associated to longevity, we assessed them in octogenarians (Old; n=42) living in the east-central mountain area of Sardinia, a High-Longevity Zone (HLZ), compared to sexagenarian (Young; n=21) subjects from the same area, and to Olds (n=22) from the Northern Sardinia indicated as Lower-Longevity Zone (LLZ). We found significant increases in conjugated linoleic acid (CLA) and heptadecanoic acid (17:0) levels in Old-HLZ with respect to younger subjects and Old-LLZ subjects. Young-HLZ subjects exhibited higher circulating levels of pentadecanoic acid (15:0) and retinol. Palmitoleic acid (POA) was elevated in both Young and Old subjects from the HLZ. eCBome profile showed a significantly increased plasma level of the two endocannabinoids, N-arachidonoyl-ethanolamine (AEA) and 2-arachidonoyl-glycerol (2-AG) in Old-HLZ subjects compared to Young-HLZ and Old-LLZ respectively. In addition, we found increased N-oleoyl-ethanolamine (OEA), 2-linoleoyl-glycerol (2-LG) and 2-oleoyl-glycerol (2-OG) levels in Old-HLZ group with respect to Young-HLZ (as for OEA an d 2-LG) and both the Old-LLZ and Young-HLZ for 2-OG. The endogenous metabolite of docosahexaenoic acid (DHA), N-docosahexaenoyl-ethanolamine (DHEA) was significantly increased in Old-HLZ subjects. In conclusion, our results suggest that in the HLZ area, Young and Old subjects exhibited a favourable, albeit distinctive, fatty acids and eCBome profile that may be indicative of a metabolic pattern potentially protective from adverse chronic conditions. These factors could point to a suitable physiological metabolic pattern that may counteract the adverse stimuli leading to age-related disorders such as neurodegenerative and metabolic diseases.

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