To assess the effects of walnuts on cardiometabolic outcomes in obese subjects and to explore underlying mechanisms using novel methods including metabolomic, lipidomic, glycomic, and microbiome analysis integrated with lipid particle fractionation, appetite-regulating hormones and hemodynamic measurements.
MATERIALS AND METHODS:
10 obese subjects were enrolled in this cross-over, randomized, double-blind, placebo-controlled clinical trial. Patients participated in two 5-day inpatient stays during which they consumed a smoothie containing 48g walnuts or a macronutrient-matched placebo smoothie without nuts, with a one-month washout period between the two visits.
Walnut consumption improved aspects of the lipid profile, i.e. reduced fasting small and dense LDL particles (p<.02) and increased postprandial large HDL particles (p<.01). Lipoprotein Insulin Resistance Score, glucose and insulin AUC decreased significantly after walnut consumption (p<.01, p<.02, p<.04, respectively). Consuming walnuts significantly increased 10 N-glycans, with 8 of them carrying a fucose core. Lipidomic analysis showed a robust reduction in harmful ceramides, hexosylceramides and sphingomyelins, which have been shown to mediate effects on cardiometabolic risk. Peptide YY AUC significantly increased after walnut consumption (p<.03). No major significant changes in hemodynamic, metabolomic analysis or in host health-promoting bacteria such as Faecalibacterium were found.
These data provide a more comprehensive mechanistic perspective of the effect of dietary walnut consumption on cardiometabolic parameters. Lipidomic and lipid nuclear magnetic resonance spectroscopy analysis showed an early but significant reduction in ceramides and other atherogenic lipids with walnut consumption that may explain the longer-term benefits of walnuts on insulin resistance, cardiovascular risk and mortality. This article is protected by copyright. All rights reserved.
High levels of proinflammatory cytokines have been associated with a loss of tissue function in ocular autoimmune diseases, but the basis for this relationship remains poorly understood. Here we investigate a new role for tumor necrosis factor α in promoting N-glycan-processing deficiency at the surface of the eye through inhibition of N-acetylglucosaminyltransferase expression in the Golgi. Using mass spectrometry, complex-type biantennary oligosaccharides were identified as major N-glycan structures in differentiated human corneal epithelial cells. Remarkably, significant differences were detected between the efficacies of cytokines in regulating the expression of glycogenes involved in the biosynthesis of N-glycans. Tumor necrosis factor α but not IL-1β had a profound effect in suppressing the expression of enzymes involved in the Golgi branching pathway, including N-acetylglucosaminyltransferases 1 and 2, which are required for the formation of biantennary structures. This decrease in gene expression was correlated with a reduction in enzymatic activity and impaired N-glycan branching. Moreover, patients with ocular mucous membrane pemphigoid were characterized by marginal N-acetylglucosaminyltransferase expression and decreased N-glycan branching in the conjunctiva. Together, these data indicate that proinflammatory cytokines differentially influence the expression of N-glycan-processing enzymes in the Golgi and set the stage for future studies to explore the pathophysiology of ocular autoimmune diseases.