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

Ninglin Wang; Yuan Ru; Zhiying Yang; Changxuan Sun; Shanshan Li; Yan Min; Xueyin Zhao; Ying Lu; Ann W Hsing; Shankuan Zhu

doi:10.3389/fnut.2021.740435

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

Front Nutr. 2021 Nov 17:8:740435. doi: 10.3389/fnut.2021.740435. eCollection 2021.

Authors

Ninglin Wang^{1

2}, Yuan Ru^{1

2}, Zhiying Yang^{1

2}, Changxuan Sun^{1

2}, Shanshan Li^{1

2}, Yan Min³, Xueyin Zhao^{1

2}, Ying Lu⁴, Ann W Hsing^{3

5

6}, Shankuan Zhu^{1

2}

Affiliations

¹ Chronic Disease Research Institute, The Children's Hospital and National Clinical Research Center for Child Health, School of Public Health, School of Medicine, Zhejiang University, Hangzhou, China.
² Department of Nutrition and Food Hygiene, School of Public Health, School of Medicine, Zhejiang University, Hangzhou, China.
³ Stanford Prevention Research Center, Department of Medicine, Stanford School of Medicine, Stanford University, Stanford, CA, United States.
⁴ Department of Biomedical Data Sciences, Stanford School of Medicine, Stanford, CA, United States.
⁵ Department of Epidemiology and Population Health, Stanford School of Medicine, Stanford, CA, United States.
⁶ Stanford Cancer Institute, School of Medicine, Stanford University, Stanford, CA, United States.

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).

Keywords: dyslipidemia; metabolomics profiles; pathway analysis; plasma retinol; vitamin A.