A biochemical basis for depressed ketogenesis in sepsis.
Several investigators have demonstrated a diminished rate of ketogenesis during inflammatory or infectious states despite the availability of free fatty acids supplied to the liver. The biochemical mechanism for this effect is unknown. Malonyl-CoA has been proposed to be a regulator of ketogenesis. Malonyl-CoA levels are low in states of rapid ketogenesis such as starvation or diabetes and high in states of reduced ketogenesis such as carbohydrate feeding. In the present study, the effect of an intra-abdominal abscess on the level of hepatic malonyl-CoA was investigated in four groups of animals (fed control, sterile inflammation, small chronic septic abscess, large chronic septic abscess). Liver samples were frozen in situ 5 days following the intraperitoneal introduction of a rat-fecal agar pellet inoculated with a known bacterial flora which generated an abscess [sterile inflammatory; B. fragilis 10(8)/ml + E. coli 10(2)/ml (small, 0.8 ml or large, 1.5 ml) abscess pellet]. The level of malonyl-CoA in normal fed rats was 5.0 +/- 0.6 nmol/gm wet wt (n = 9). The malonyl-CoA level was not altered in animals with a sterile inflammation. However, hepatic malonyl-CoA levels were significantly increased in small (10 +/- 1 nmole/gm wet wt) (p less than 0.05; n = 9) or large (12 +/- 1 nmol/gm wet wt) (p less than 0.01; n = 14) septic abscess rats compared to control fed and sterile inflammatory rats. Hepatic ketone bodies (beta-hydroxybutyrate and acetoacetate) did not increase in sepsis over control or sterile inflammation.(ABSTRACT TRUNCATED AT 250 WORDS)
Vary
T C
TC
Siegel
J H
JH
Nakatani
T
T
Sato
T
T
Aoyama
H
H
D000105:Acetyl Coenzyme A / Q000032:analysis; D000818:Animals; D002332:Carnitine O-Acetyltransferase / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism; D007239:Infections / Q000378:metabolism*; D007657:Ketone Bodies / Q000032:analysis / Q000096:biosynthesis* / Q000378:metabolism; D008099:Liver / Q000032:analysis / Q000378:metabolism; D008297:Male; D008316:Malonyl Coenzyme A / Q000032:analysis / Q000378:metabolism; D010084:Oxidation-Reduction; D051381:Rats; D011919:Rats, Inbred Strains
D005227:Fatty Acids; D007657:Ketone Bodies; D008316:Malonyl Coenzyme A; D000105:Acetyl Coenzyme A; D002332:Carnitine O-Acetyltransferase