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Metabolomic Profiles of Plasma Retinol-Associated Dyslipidemia in Men and Women.

ABSTRACT: Background and Aims: Studies of both animals and humans show that a high intake of vitamin A is associated with a lower risk of dyslipidemia. However, an association of plasma retinol levels with dyslipidemia is unclear. Therefore, the aim of this study is to investigate an association between plasma retinol and dyslipidemia and to identify related metabolites and pathways in the general population. Methods: We included 250 participants aged 20-80 years from the Wellness Living Laboratory (WELL) China cohort. Associations between plasma retinol levels and dyslipidemia were analyzed using adjusted logistic models. Related metabolites were identified using ANCOVA, adjusted for the false discovery rate (FDR) and used for pathway analyses. Because there are sex differences in plasma retinol levels, all analyses were conducted separately by sex. Results: Plasma retinol was significantly higher in men than in women. A positive association between plasma retinol and dyslipidemia was found in both sexes. In men, the 2nd and 3rd tertiles showed significantly higher proportions of dyslipidemia than the 1st tertile (1st tertile vs. 2nd tertile: p = 0.026; 1st tertile vs. 3rd tertile: p = 0.003). In women, the 3rd tertile showed a significantly higher proportion of dyslipidemia than the 1st and 2nd tertile (3rd tertile vs. 1st tertile: p = 0.002, 3rd tertile vs. 2nd tertile: p = 0.002). Overall, 75 and 30 metabolites were significantly associated with retinol levels in men and women, respectively. According to these metabolites, lipid metabolic pathways, including glycerophospholipid, arachidonic acid, linoleic acid, alpha-linolenic acid, and glycosylphosphatidylinositol (GPI), as well as steroid hormone biosynthesis pathways were found to overlap across the sexes. These pathways showed that elevated retinol levels might be associated with hormone metabolism and inflammation status. Conclusions: We found a positive association between plasma retinol levels and dyslipidemia. Related metabolomic profiles and interrupted pathways showed that such an increase might be associated with steroid hormone synthesis and inflammation. In addition, large, population-based longitudinal studies and intervention studies are needed to confirm the role of retinol in lipid metabolism and the prevention of cardiovascular disease (CVD).

SUBMITTER: Wang N

PROVIDER: S-EPMC8635783 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:In epidemiologic studies, human immunodeficiency virus (HIV)-infected men on antiretroviral therapy (ART) are at higher risk of incident diabetes mellitus compared with women with similar treatment histories. We used metabolomics to determine whether a sex difference in plasma amino acids, acylcarnitines, and organic acids predictive of diabetes and impaired energy metabolism is present in HIV-infected persons on long-term ART.We enrolled 70 HIV-infected adults (43% women) on efavirenz, tenofovir, and emtricitabine (Atripla) with HIV-1 RNA <50?copies/mL for over 2 years. Half of the HIV-infected subjects were obese, and these were matched with 30 obese HIV-negative controls. All subjects had no history of diabetes, statin use, or heavy alcohol use. Fasting insulin sensitivity was measured using homeostatic model assessment 2 (HOMA2), and adipose tissue was measured using dual-energy x-ray absorptiometry (DEXA). Liquid chromatography/mass spectrometry was used to quantitate fasting plasma branched chain and aromatic amino acids predictive of incident diabetes, and C3 and C5 acylcarnitinines and organic acids indicative of impaired energy metabolism.HIV-infected women had more baseline risk factors for insulin resistance: women were older (46 vs 44 years) and had a longer ART duration (8.4 vs 5.1 years, P?<?0.05 for both) compared with men but had similar CD4+ count (median 701?cells/?L), smoking and hepatic C prevalence, and body mass index (BMI) (median 30.3?kg/m). However, women had higher insulin sensitivity compared with men (P?<?0.01), and lower plasma levels of isoleucine, leucine, valine, phenylalanine, and tyrosine (P?<?0.01 for all), and lower C3 and C5 acylcarnitines (P?<?0.01 for all), in multivariable regression models after adjusting for DEXA fat mass index, age, race, CD4+ count, smoking, and ART duration. In the obese HIV-infected subjects and HIV-negative controls, the relationship of sex and plasma metabolite levels did not significantly differ according to HIV-status.HIV-infected women on non-nucleoside reverse transcriptase inhibitor-based ART had superior glucose tolerance and lower plasma metabolites associated with the development of diabetes compared with men with similar metabolic disease risk profiles. The relationship between sex and plasma metabolite levels did not significantly differ according to HIV-status among obese subjects, suggesting the observed sex-differences may not be specific to HIV infection.

Project description:BackgroundWe previously showed that a food-based empirical dietary inflammatory pattern (EDIP) score is associated with circulating inflammatory biomarkers. Metabolomic profiling of inflammatory diets may therefore provide insights on mechanisms contributing to disease etiology and prognosis. We aimed to elucidate metabolites associated with inflammatory diets among postmenopausal women, utilizing a robust study design that incorporates independent discovery and validation datasets.MethodsThis baseline cross-sectional investigation evaluated associations between continuous EDIP scores calculated from food frequency questionnaires and 448 log-transformed plasma metabolites as outcomes in multivariable-adjusted linear regression analyses. Metabolites were measured with liquid chromatography tandem mass spectroscopy. Metabolite discovery was conducted among 1109 Women's Health Initiative (WHI) Hormone Therapy trial participants and results were replicated in an independent dataset of 810 WHI Observational Study participants. Secondary analyses were stratified by standard body mass index (BMI, kg/m2) categories. In discovery and replication datasets statistical significance was based on false-discovery rate adjusted P < 0.05.ResultsAfter adjusting for energy intake, BMI, physical activity, and other confounding variables, 23 metabolites were significantly associated with EDIP score in the discovery dataset. Of these, the following ten were replicated: trigonelline, caffeine, acethylamino-6-amino-3-methyluracil, 7-methylxanthine, 1,7-dimethyluric acid, 3-methylxanthine, C18:3CE, glycine, associated with lower dietary inflammatory potential; whereas C52:3 triacylglycerol and linoleate associated with higher dietary inflammatory potential. Four of the ten were associated [glycine (inversely), caffeine, 1,7-dimethyluric acid, C52:3 triacylglycerol, (positively)], with C-reactive protein levels. In secondary analyses, associations showed differences by BMI category. Four metabolites, related to coffee/caffeine metabolism were inversely associated among normal weight women, and 83 metabolites associated with EDIP among overweight/obese women, including 40 (48%) that were also associated with C-reactive protein.ConclusionMetabolites associated with coffee/caffeine and lipid metabolism may reflect the inflammatory potential of diet. Potential differences by BMI and the linkage to disease outcomes, require further study.

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Metabolomic Profiles of Plasma Retinol-Associated Dyslipidemia in Men and Women.

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