The effect of Escherichia coli endotoxin on the adrenergic control of lipolysis in the human adipocyte.
We investigated the effect of Escherichia coli O127:B8 endotoxins on the adrenergic control of lipolysis in the human adipocyte. Adipose tissue was incubated in vitro with isoproterenol to stimulate the beta-1 receptors, clonidine to stimulate the alpha-2 receptors, and theophylline to stimulate the subreceptor mechanism. Using a dual radioisotope technique, a lipolysis factor was calculated for each sample. The basal lipolysis factor was significantly (P less than 0.006) decreased 31% with endotoxin. beta-1 adrenergic receptor stimulation (isoproterenol, 1 X 10(-8) to 1 X 10(-4) M) was significantly decreased an average of 31% with E. coli endotoxin. The beta-1 receptor responsiveness was also significantly (P less than 0.02) decreased but not the receptor sensitivity. This indicated an alteration in the post beta receptor mechanism. The various components of the post beta-1 adrenergic mechanism were stimulated including the beta-1 receptor, the G protein, adenylase cyclase, and the lipase phosphorylase. The results indicated a significant 24.2% reduction of the beta-1 receptor and a 25.4% reduction in G protein stimulation. Thus the E. coli endotoxin effect on the beta adrenergic mechanism is at the G protein. The endotoxin had no effect on the alpha-2 receptor stimulation nor the theophylline stimulation of the subreceptor lipolysis. This study indicates that E. coli endotoxin (O127:B8) decreases in vitro beta adrenergic stimulation of human adipocyte lipolysis, and this effect can be partially reversed by theophylline.
Forse
R A
RA
Department of Surgery, McGill University, Montreal, Quebec, Canada.
Leibel
R
R
Gagner
M
M
D000273:Adipose Tissue / Q000378:metabolism*; D002772:Cholera Toxin / Q000494:pharmacology; D003000:Clonidine / Q000494:pharmacology; D004731:Endotoxins / Q000494:pharmacology*; D004926:Escherichia coli; D005260:Female; D019204:GTP-Binding Proteins / Q000502:physiology; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology; D008066:Lipolysis / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000502:physiology*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000502:physiology*; D013806:Theophylline / Q000494:pharmacology
D004731:Endotoxins; D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; C044101:endotoxin, Escherichia coli; D002772:Cholera Toxin; D013806:Theophylline; D019204:GTP-Binding Proteins; D007545:Isoproterenol; D003000:Clonidine