Adipocyte functions are modulated by cell size change: potential involvement of an integrin/ERK signalling pathway.

Abstract

Adipocyte is the only cell whose size may vary dramatically in physiological conditions. We hypothesized that increase in fat cell size per se could modulate several signalling pathways by changing the relationships between the cell and the extracellular matrix. The aim of the current study was (i). to examine whether within the same fat depot, metabolic functions of adipocyte were modified by cell size and (ii). if such an adaptation exists, to look for an integrin/extracellular-signal-regulated kinases (ERKs) signalling pathway. We isolated two populations of adipocytes with different volumes (67 and 22 x 10(3) microm(3)) within the same adipose location. In large compared to small fat cells, fatty acid synthase and lipoprotein lipase activities were increased two- and seven-fold, respectively; GLUT4 protein concentration and leptin expression were increased three-fold; lipolytic capacity was increased four-fold. The integrin/ERK signalling pathway could be the one responsible for the adaptation of adipose functions to cell size. In large compared with small adipocytes, we showed that beta(1)-integrins are present in adipose membranes and at a higher concentration in large than in small cells. In isolated adipocytes, stimulation of beta(1)-integrins with a specific monoclonal antibody results in ERK(1) and ERK(2) activation. In large compared to small cells, cytoplasmic concentrations of these two mitogen-activated protein kinases were increased two-fold, whereas their activities were increased 10-fold. A beta(1)-integrin/ERKs signalling pathway is present in mature adipocyte. Increase in cell size, by modifying the relationships between cell and extracellular matrix, could turn on this pathway. Since ERKs can modulate transcription factors and subsequently modulate gene expression important for adipose function, this pathway could play an important role in the adaptation of adipose functions to cell size.