INSULIN STIMULATES LIPOPROTEIN-LIPASE ACTIVITY AND SYNTHESIS IN ADIPOCYTES FROM SEPTIC RATS

Gram-negative sepsis suppresses lipoprotein lipase (LPL) activity in a dipose tissue which contributes, in part, to the altered clearance of triglycerides. The suppression in LPL activity occurs when plasma insu lin concentrations are elevated and insulin-stimulated glucose utiliza tion is impaired. This study was planned to evaluate whether the prese nce of insulin resistance was responsible for the decrease in adipose LPL activity. Adipocytes were isolated from epididymal fat pads 24 h a fter inducing sepsis in male Lewis rats by intravenous injection of 4 x 10(8) colonies of live Escherichia coli/100 g body wt. The decrease in heparin-releasable (HR) LPL activity in adipocytes from the septic rats was evident at the time of isolation and maintained in a 20-h cul ture. After overnight incubation with insulin (10(-8) M), HR LPL activ ity was stimulated to a greater extent in adipocytes from septic rats (298%) than in adipocytes from control rats (88%). The insulin stimula tion of LPL activity during sepsis could not be attributed to insulin- like growth factor-I (IGF-I) as adipocytes from septic rats appeared t o be IGF-I resistant. Insulin-treatment (10(-8) M) increased LPL synth esis 99% in adipocytes from control rats and 136% in adipocytes from s eptic rats. Insulin treatment also led to a 65 and 62% increase in LPL mass in adipocytes from control and septic rats, respectively. These findings indicate that the sepsis-induced decrease in adipose LPL is n ot due to insulin resistance with respect to LPL. The insulin stimulat ion of LPL activity in adipocytes from septic rats appears to be media ted by an increase in LPL synthesis. (C) 1997 Academic Press.