Endotoxin-Induced Alterations in Isolated Fat Cells: Effect on Norepinephrine-Stimulated Lipolysis and Cyclic 3′,5′-Adenosine Monophosphate Accumulation

Abstract

Summary

This study was designed to investigate the mechanism of interaction between endotoxin and isolated canine fat cells. Exposure to endotoxin in vitro elicited a higher NE-stimulated lipolytic response than that obtained from normal cells. The release of G and FFA in both normal and endotox-in-treated cells was linear for 2 hr.

NE dose–response studies revealed increased G and FFA release at each dose level including saturation, after endotoxin treatment, without consistent changes in the dose at which half-maximal response occurred. The NE dose–response curves were compatible with the Clark-Stetton model of hormone action. Thus the data are consistent with the interpretation of a greater number of receptor—hormone complexes being involved after exposure to endotoxin. Endotoxin-treated fat cells of both SC and O origin had a significantly higher cAMP level, which was further elevated by subsequent NE stimulation, manyfold above the level of normal cells.

The results suggest that exposure of isolated fat cells to endotoxin in vitro causes alterations in the lipoprotein components as well as in the ionic distribution within the fat cell membrane.

This investigation was supported by NIH Grant HL 03130 and ONR contract no. 108-969. The author is grateful to Dr. Howard Rasmussen of the University of Pennsylvania School of Medicine for helpful discussion of some of these data. Richard Storck provided valuable technical assistance.