Combined Analysis of Stress‐ and ECM‐Related Genes in Their Effect on Weight Regain

Objective During weight loss, the volume of adipocytes decreases, leading to stress because of the misfit between the cell contents and the surrounding extracellular matrix (ECM). This stress can be resolved by remodeling the ECM or the restorage of triglycerides within the adipocytes. The objective of this study was to investigate the existence of a connection between stress‐related and ECM‐related genes that is associated with weight regain. Methods Thirty‐one participants with overweight or obesity followed a 5‐week very‐low‐calorie diet (500 kcal/d) with a subsequent 4‐week weight‐stable diet (WS), and then an uncontrolled 9‐month follow‐up. Adipose tissue biopsies were collected for microarray analysis. A correlation and interaction analysis was performed with the weight regain percentage (WR%) ([weight after follow‐up − weight after WS] ÷ weight after WS × 100%) by using two gene sets that were previously defined as “stress‐related” (n = 107) and “ECM‐related” genes (n = 277). Results During WS, a coexpression network of 8 stress‐related genes and 15 ECM‐related genes correlating with WR% could be constructed, with links to multiple biological processes. Interaction analysis between stress‐ and ECM‐related genes revealed that several gene combinations were highly related to weight regain. Conclusions Our findings underscore the importance of the connection between stress‐ and ECM‐related genes in the risk for weight regain.