Altered ketone body metabolism during gram-negative sepsis in the rat.
To investigate why blood ketone bodies are depressed during sepsis, the production and utilization of ketone bodies was studied in fasted control, fasted, Escherichia coli-treated, fed control, and fed E coli-treated rats. Gram-negative sepsis was induced by intravenous (IV) injection of 8 x 10(7) live colonies of E coli per 100 g body weight. Food was removed from the fasted rats after E coli injection. Fed rats were infused intragastrically with a nutritionally adequate diet for 5 days before inducing sepsis. Twenty-four hours after E coli injection, blood ketone bodies were reduced in fasted septic rats and fed septic rats compared with their respective control rats. Ketogenesis and oxidation of labeled palmitate was not altered in hepatocytes from fasted E coli-treated rats. Yet, ketogenesis declined significantly in hepatocytes from fed E coli-treated rats. Oxidation of labeled palmitate was also significantly reduced in hepatocytes from fed E coli-treated rats. Utilization of ketone bodies as measured by the incorporation of [3-14C]beta-hydroxybutyrate into CO2, increased over threefold in the diaphragm, 12% in the heart, and 19% in the kidneys from the fasted E coli-treated rats. In the fed state, incorporation of [3-14C]beta-hydroxybutyrate into CO2 was elevated fivefold in the heart, fourfold in the diaphragm, and over threefold in the kidneys from the septic rats. These results suggest that in the fasted state, plasma ketone bodies remain low during gram-negative sepsis because peripheral tissues use more ketone bodies and because liver ketogenesis is not increased to compensate for the increased utilization. In the fed state, the reduction in blood ketone bodies appears to be attributed to both impaired ketogenic capacity and increased peripheral utilization.
Lanza-Jacoby
S
S
Department of Surgery, Jefferson Medical College, Philadelphia, PA 19107.
Rosato
E
E
Braccia
G
G
Tabares
A
A
D000818:Animals; D004927:Escherichia coli Infections / Q000097:blood* / Q000378:metabolism; D005230:Fatty Acids, Nonesterified / Q000097:blood; D007657:Ketone Bodies / Q000096:biosynthesis / Q000097:blood*; D008099:Liver / Q000166:cytology / Q000378:metabolism; D008297:Male; D010084:Oxidation-Reduction; D051381:Rats; D011917:Rats, Inbred Lew
D005230:Fatty Acids, Nonesterified; D007657:Ketone Bodies