Adipose tissue sensitization to insulin induced by troglitazone and MEDICA 16 in obese Zucker rats in vivo

The putative role played by insulin sensitizers in modulating adipose tissue lipolysis in the fasting state was evaluated in obese conscious Zucker rats treated with troglitazone or β,β′-tetramethylhexadecanedioic acid (MEDICA 16) and compared with nontreated lean and obese animals. The rates of appearance (R_a) of glycerol and free fatty acid (FFA), primary intra-adipose reesterification, and secondary reuptake of plasma FFA in adipose fat were measured using constant infusion of stable isotope-labeled [²H₅]glycerol, [2,2-²H₂]palmitate, and radioactive [³H] palmitate. The overall lipolytic flux (R_a glycerol) was increased 1.7-and 1.4-fold in obese animals treated with troglitazone or MEDICA 16, respectively, resulting in increased FFA export (R_a FFA) in the troglitazone-treated rats. Primary intra-adipose reesterification of lipolysis-derived fatty acids was enhanced twofold by insulin sensitizers, whereas reesterification of plasma fatty acids was unaffected by either treatment. Despite the unchanged R_a FFA in MEDICA 16 or the increased R_a FFA induced by troglitazone, very low density lipoprotein production rates were robustly curtailed. Total adipose tissue reesterification, used as an estimate of glucose conversion to glyceride-glycerol, was increased 1.9-fold by treatment with the insulin sensitizers. Our results indicate that, in the fasting state, insulin sensitizers induce, in vivo, a significant activation rather than suppression of adipose tissue lipolysis together with stimulation of glucose conversion to glyceride-glycerol.