Abstract
ObjectiveSubjects with low vitamin D levels are at risk of cardiometabolic disease. The aim of this study was to identify novel serological markers linking vitamin D status with cardiometabolic profile in non-diabetic adults with obesity.MethodsFor the discovery phase, we used quantitative serum proteomics in sex-matched, age-matched and BMI-matched subjects with obesity [BMI: 25–35 kg/m2] and low [25(OH)D < 50 nmol/L] vs. high vitamin D status [25(OH)D > 50 nmol/L] (n = 16). For the validation phase, we performed ELISA in a larger cohort with similar characteristics (n = 179).ResultsWe identified 423 and 549 differentially expressed proteins in the high vs. low vitamin D groups of the male and female cohorts, respectively. The small molecule biochemistry protein networks and the glycolysis|gluconeogenesis pathway were significantly enriched in the DEPs of both sexes. As surrogate markers to these processes, the insulin-like growth factor binding protein -2 (IGFBP-2) was upregulated in males, whereas IGFBP-3 was upregulated in females from the high Vitamin D status. This sex-specific trend was confirmed using Luminex ELISA to an independent but clinically analogous cohort of males (n = 84, p = 0.002) and females (n = 95, p = 0.03).ConclusionsThe high Vitamin D status correlated with the serological upregulation of IGFBP-2 in males and IGFBP-3 in females with obesity and may constitute surrogate markers of risk reduction of cardiometabolic disease.
Highlights
Introduction VitaminD is an ancient hormone, originally produced by archaebacteria, phytoplankton and zooplankton datingNutrition and DiabetesAl-Daghri et al Nutrition and Diabetes (2018)8:54 nmol/L4
The low and high vitamin D status groups of the male and female participants were similar with regards to age, BMI, fasting glucose, sun exposure, physical activity and total energy, DHA/EPA and calcium intake
KEGG canonical pathway analysis showed that glycolysis| gluconeogenesis was significantly enriched in the differentially expressed proteins (DEPs) of the male and female cohorts (Fisher exact p = 0.002 and 0.028, respectively for males and females) (Fig. 3c)
Summary
Introduction VitaminD is an ancient hormone, originally produced by archaebacteria, phytoplankton and zooplankton datingNutrition and DiabetesAl-Daghri et al Nutrition and Diabetes (2018)8:54 nmol/L4. The Endocrine Society suggested that circulating 25(OH)D should be maintained at higher concentrations (75 to 80 nmol/L) for extra-skeletal health benefits[5] with no known toxicity at this level[6,7]. A meta-analysis, including 65,000 prospectively monitored participants, showed that the group with the lowest compared to the highest serum 25(OH)D levels had a relative risk of 1.5 (1.3 to 1.8) for total incidents of cardiovascular disease and 1.6 (1.3 to 2.1) for stroke[10]. Another meta-analysis of approximately 500,000 participants found an inverse association with allcause mortality for circulating 25(OH)D levels up to 75 nmol/L11. Decreased 25(OH)D levels may affect cardiovascular risk either directly, for example by increasing blood pressure through the renin-angiotensin system, or indirectly, by influencing inflammation, myocardial function, vascular calcification and parathyroid hormone levels[13]
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