A data integration multi-omics approach to study calorie restriction-induced changes in insulin sensitivity

The mechanisms responsible for weight loss-induced improvement in insulin sensitivity are partially understood. Greater insight can now be achieved through deep phenotyping and data integration. Here, we used an integrative approach to investigate associations between changes in insulin sensitivity and variations in lifestyle factors (diet and physical activity), subcutaneous adipose tissue (sAT) gene expression, metabolomics in serum, urine and feces, and gut microbiota composition after a 6-week calorie restriction period in overweight and obese adults. A spectrum of variables from lifestyle factors, gut microbiota and host multi-omics most associated with insulin sensitivity was identified. These analyses highlight associations between variations in insulin sensitivity, serum branched chain amino acids, sAT genes involved in endoplasmic reticulum stress and ubiquitination, and gut metagenomic species. This work has enhanced previous knowledge on mechanistic links between host glucose homeostasis, lifestyle factors and microbiota, and has identified modifiable factors and biomarkers that may be used to predict and improve individual response to weight loss interventions.