Weight Loss

Biography

Biography: Edwin C.M. Mariman

Abstract

Overweight is one of the major problems of modern day societies. Although weight reduction is fairly easy, maintenance of the reduced weight is the true challenge. Research has mainly focussed on psychosocial factors as a cause for weight regain, but also biological factors may play a role. We are investigating the possibility that adipocytes act as driving force behind weight regain after weight loss. Mature adipocytes are surrounded by a strong extracellular matrix (ECM). When adipocytes shrink during weight loss, the ECM should adjust in parallel. However, under conditions of energy restriction, this process is hampered, leading to mechanical stress between the adipocyte and the surrounding ECM. We hypothesize that this adipocyte cellular stress is a promoter of weight regain. Using genetic variation in 124 ECM genes as part of the pan-European DiOGenes GWAS, association was found between the risk for weight regain and five ECM genes. In addition, we quantified eight stress proteins in adipose tissue and found some of them to be significantly increased in persons who regained weight, but not in persons who remained weight stable. Together this supports our hypothesis. Moreover, we found that adipocytes during weight loss or shortly thereafter, increase their capacity for fat uptake and storage. A model for weight regain will be presented in which adipocytes try to get rid of their cellular stress by lowering the secretion of leptin to induce food intake by the host followed by re-filling of the adipocytes. As a consequence the host will regain weight.