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BIONÆR-Bionæringsprogram

METADIS: STAY Sulfur amino acids, energy metabolism and obesity

Alternative title: Svovelaminosyrer, energimetabolisme og fedme

Awarded: NOK 5.8 mill.

The prevalence of overweight and obesity are increasing worldwide. World Health Organization report that that 1.9 billion people were overweight and 650 million were obese in 2016. Obesity leads to increased risk of chronic diseases and mortality. Over the last few years, two amino acids, methionine and cysteine, have been associated with development of obesity and related metabolic diseases. In rodents, experiments with diets low in methionine and cysteine content result in improved glucose and lipid metabolism and reduced body fat. In the STAY project, we will examine the role of cysteine and methionine and related compounds in human metabolic health and obesity. In March 2021, we initiated a dietary intervention study in participants with overweight and obesity to evaluate the effects of a plant-based diet low in methionine and cysteine on body weight, body composition, and energy balance, as well as obesity-related blood markers (glucose and lipid metabolism, amino acids, fatty acids). A total of 61 participants were randomized to the intervention, and the data collection was completed March 2022. Preliminary results indicate effects on body weight and on several biomarkers in plasma and urine. In addition, we use data from a large Dutch population study to investigate associations of dietary, circulating and urinary methionine and cysteine with body fat and disease. We have performed several analyses for the determination of amino acids, appetite hormones and fatty acid profiles in biological material. Statistical analyses on data from the diet intervention and the population study are ongoing and results will be published through 2022 and 2023. The first original article was published in November 2022 (doi: 10.1007/s00394-022-03041-4) on the associations of plasma concentrations of methionine and cysteine with different fat depots. This project will give us insight into the role of methionine and cysteine in human metabolic health and obesity development.

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Overweight and obesity lead to metabolic disturbances and increase the overall risk of morbidity and mortality. In the past decade, circulating amino acids have become increasingly recognized as predictors of metabolic risk. Recently, the sulfur-containing amino acids (SAA) methionine and cysteine have been suggested to play roles in development of obesity and related metabolic disease. In animals, dietary restriction of SAA increases insulin sensitivity and reduces adiposity. Research in STAY comprises human interventional and epidemiologic studies to establish the role of dietary, circulating and urinary sulfur amino acids and related compounds as modifiable risk factors in human metabolic health and obesity. We will perform a dietary intervention study in participants with overweight and obesity to evaluate effects of a SAA restricted plant-based diet on body fatness and energy balance, as well as biomarkers and gene expression patterns related to energy metabolism. In addition, we will use data from a large Dutch cohort to investigate whether dietary patterns are associated with SAA in plasma and urine, and with body fat, morbidity and mortality. Genetic data from this cohort will be used to investigate gene-nutrient interactions. The project will use state-of-the-art methodology to assess plasma and urine amino acids, plasma lipids and fatty acid profiles, glucose tolerance, adipokines and appetite-related hormones. Overall, the project can potentially translate the well-described beneficial findings of dietary SAA restriction in animals to humans with obesity. Research in STAY will provide unique insight into the SAA-mediated regulation of energy metabolism, appetite, obesity and metabolic disease. Because an SAA restricted diet is largely plant-based, the STAY project will enhance understanding of the mechanisms by which a plant-based diet low in SAA content can benefit human metabolic health.

Funding scheme:

BIONÆR-Bionæringsprogram