Abstract
Sphingolipid metabolism plays a critical role in cell growth regulation, lipid regulation, neurodevelopment, type 2 diabetes, and cancer. Animal experiments suggest that vitamin D may be involved in sphingolipid metabolism regulation. In this study, we tested the hypothesis that vitamin D supplementation would alter circulating long-chain ceramides and related metabolites involved in sphingolipid metabolism in humans. We carried out a post-hoc analysis of a previously conducted randomized, placebo-controlled clinical trial in 70 overweight/obese African-Americans, who were randomly assigned into four groups of 600, 2000, 4000 IU/day of vitamin D3 supplements or placebo for 16 weeks. The metabolites were measured in 64 subjects (aged 26.0 ± 9.4 years, 17% male). Serum levels of N-stearoyl-sphingosine (d18:1/18:0) (C18Cer) and stearoyl sphingomyelin (d18:1/18:0) (C18SM) were significantly increased after vitamin D3 supplementation (ps < 0.05) in a dose–response fashion. The effects of 600, 2000, and 4000 IU/day vitamin D3 supplementation on C18Cer were 0.44 (p = 0.049), 0.52 (p = 0.016), and 0.58 (p = 0.008), respectively. The effects of three dosages on C18SM were 0.30 (p = 0.222), 0.61 (p = 0.009), and 0.68 (p = 0.004), respectively. This was accompanied by the significant correlations between serum 25-hydroxyvitamin D3 [25(OH)D] concentration and those two metabolites (ps < 0.05). Vitamin D3 supplementations increase serum levels of C18Cer and C18SM in a dose–response fashion among overweight/obese African Americans.
Highlights
Sphingolipids are bioactive lipids and key components of cell membranes, which exert critical roles in signal transduction [1]
To the best of our knowledge, only one randomized controlled trial (RCT) has been conducted, which reports that vitamin D supplementation regulates sphingolipid metabolism in a European population with type 2 diabetes [15]
The present study shows that vitamin D3 supplementations increase serum levels of long-chain
Summary
Sphingolipids are bioactive lipids and key components of cell membranes, which exert critical roles in signal transduction [1]. Ceramide (Cer), composed of a sphingosine backbone N-acylated with different fatty acyl-CoA [7], is a multifunctional central molecule in sphingolipid metabolism. Studies suggest that vitamin D supplementation may improve glycemic controls and insulin sensitivity [11,12]. Animal experiments suggest that vitamin D may be involved in sphingolipid metabolism regulation [20]. To the best of our knowledge, only one randomized controlled trial (RCT) has been conducted, which reports that vitamin D supplementation regulates sphingolipid metabolism in a European population with type 2 diabetes [15]. In this study, for the first time, we tested the hypothesis that vitamin D supplementation would alter the sphingolipid metabolism in a dose–response fashion among overweight/obese African Americans by a post-hoc analysis of a previously conducted RCT
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