Weight Loss-induced Interaction Between Classical Lipolysis and the Autolysosome in Human Subcutaneous Adipose Tissue

Abstract Background/objectives:During a period of weight loss lipolysis genes in human subcutaneous adipose tissue are downregulated despite the increase in plasma free fatty acids. It has been proposed that lipid breakdown is taken over by the autolysosome. Here we test the relation between lipolysis and the autolysosome. Subjects/methods:Gene and protein expression data from the YoYo-study were used for correlation analysis including genes coding for lipases and regulators of lipolysis, for autolysosome proteins and lysosomal enzymes, and the genes coding for components of a previously identified integrin cluster. For all these genes the cell type and compartment of expression was obtained from databases. Correlation analysis was performed using the gene expression values before weight loss (WL), after WL, and after a subsequent weight stable period (WS), and using the expression changes during WL and WS. Results:During WL a significant negative correlation originated between the lipolysis and autolysosome genes. Genes of the integrin cluster correlated negative with the lipolysis genes and positive with the autolysosome genes. Surprisingly, the lipolysis genes were expressed in mature adipocytes while the autolysosome genes were not, but were expressed in other types of cells of the adipose tissue. Most of the correlated autolysosome genes were secreted or on the plasma membrane. After WL most of the genes reversed their direction of expression. During WS the correlation between lipolysis and autolysosome genes lost significance and the correlation with the integrin genes disappeared. Conclusions:Our findings do not support a transfer of lipid breakdown from lipolysis to the autolysosome in subcutaneous adipocytes during WL. Instead, we observe an intercellular interaction between lipolysis in mature adipocytes and the autolysosome of other cells in the adipose tissue. This interaction is probably mediated by integrin-mediated contact between the cells. A model for the observed interaction based on ECM-stress is presented.