Higher plasma serine levels are associated with favorable values of metabolic health markers among middle-aged and older adults in The Maastricht Study
摘要
Laboratory studies indicate a mechanistic role for serine in the metabolic benefits induced by dietary restriction of methionine and cysteine. To investigate the association of plasma serine with metabolic health markers in humans, we conducted a cross-sectional analysis of a subset of data from The Maastricht Study (n = 1199). Linear regression analyses (adjusted for confounding variables) were conducted to investigate whether plasma serine is associated with markers of lipid metabolism, glucose homeostasis, and body composition. Interaction analyses were conducted to investigate whether sex, diabetes status, and plasma total cysteine modify the association of serine with metabolic markers. Correlations between dietary intake of sulfur amino acids and plasma amino acids, including methionine and total cysteine, were also investigated. Elevated plasma serine was associated with favorable changes in markers of lipid metabolism (triglycerides, total cholesterol, and indices of multiple fatty acid desaturases), glucose homeostasis (insulin resistance and glucose tolerance), fat utilization (β-hydroxybutyrate, acetoacetate, and acetone), and body composition (visceral and subcutaneous adipose depots, liver fat, and body mass index). Some associations were stronger in males than in females and in individuals with prediabetes and diabetes than in those without diabetes. Associations of plasma serine with body mass index, total fat mass, total lean mass, and subcutaneous adipose tissue weakened as plasma cysteine increased. Combined methionine and cysteine intake was inversely associated with plasma serine. Findings suggest that plasma serine is strongly associated with improved metabolic health in humans. Additional studies are required to confirm whether the associations are causal.
Graphical abstractArrow 1: We previously reported that decreasing the dietary intake of sulfur amino acids increases plasma and hepatic serine and confers several metabolic health benefits in rodents (Nichenametla et al. 2022;21(12):e13739, Aging Cell).Arrow 2: In the present study, we hypothesized that plasma serine is associated with metabolic health markers in humans. Arrow 3: To test our hypothesis, A) we selected a subset of the population from the well-characterized and deeply phenotyped human study, The Maastricht Study. B) Multiple linear regression analyses after adjusting for confounders (age, sex, type-2 diabetes status, education, smoking, alcohol intake, total energy intake, physical activity, and plasma creatinine) show that plasma serine is associated with several metabolic health markers in humans (dots and lines represent regression coefficients and 95% confidence intervals) and that C) some of these associations are affected by sex, type-2 diabetes status, and plasma cysteine concentrations.