Dietary sulfur amino acid restriction in humans with overweight and obesity: a translational randomized controlled trial.

BACKGROUND: Dietary sulfur amino acid restriction (SAAR) improves metabolic health in animals. In this study, we investigated the effect of dietary SAAR on body weight, body composition, resting metabolic rate, gene expression profiles in white adipose tissue (WAT), and an extensive blood biomarker profile in humans with overweight or obesity. METHODS: N = 59 participants with overweight or obesity (73% women) were randomized stratified by sex to an 8-week plant-based dietary intervention low (~ 2 g/day, SAAR) or high (~ 5.6 g/day, control group) in sulfur amino acids. The diets were provided in full to the participants, and both investigators and participants were blinded to the intervention. Outcome analyses were performed using linear mixed model regression adjusted for baseline values of the outcome and sex. RESULTS: SAAR led to a ~ 20% greater weight loss compared to controls (ß 95% CI - 1.14 (- 2.04, - 0.25) kg, p = 0.013). Despite greater weight loss, resting metabolic rate remained similar between groups. Furthermore, SAAR decreased serum leptin, and increased ketone bodies compared to controls. In WAT, 20 genes were upregulated whereas 24 genes were downregulated (FDR < 5%) in the SAAR group compared to controls. Generally applicable gene set enrichment analyses revealed that processes associated with ribosomes were upregulated, whereas processes related to structural components were downregulated. CONCLUSION: Our study shows that SAAR leads to greater weight loss, decreased leptin and increased ketone bodies compared to controls. Further research on SAAR is needed to investigate the therapeutic potential for metabolic conditions in humans. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT04701346, registered Jan 8th 2021, https://www. CLINICALTRIALS: gov/study/NCT04701346.

Transcriptome and metabolome analysis of citrus fruit to elucidate puffing disorder.

A systems-level analysis reveals details of molecular mechanisms underlying puffing disorder in Citrus fruit. Flavedo, albedo and juice sac tissues of normal fruits and fruits displaying symptoms of puffing disorder were studied using metabolomics at three developmental stages. Microarrays were used to compare normal and puffed fruits for each of the three tissues. A protein-protein interaction network inferred from previous work on Arabidopsis identified hub proteins whose transcripts show significant changes in expression. Glycolysis, the backbone of primary metabolism, appeared to be severely affected by the disorder, based on both transcriptomic and metabolomic results. Significantly less citric acid was observed consistently in puffed fruits. Gene set enrichment analysis suggested that glycolysis and carbohydrate metabolism were significantly altered in puffed samples in both albedo and flavedo. Expression of invertases and genes for sucrose export, amylose-starch and starch-maltose conversion was higher in puffed fruits. These changes may significantly alter source-sink communications. Genes associated with gibberellin and cytokinin signaling were downregulated in symptomatic albedo tissues, suggesting that these hormones play key roles in the disorder. Findings may be applied toward the development of early diagnostic methods based on host response genes and metabolites (i.e. citric acid), and toward therapeutics based on hormones.