Role of the liver in regulation of ketone body production during sepsis.
During caloric deprivation, the septic host may fail to develop ketonemia as an adaptation to starvation. Because the plasma ketone body concentration is a function of the ratio of hepatic production and peripheral usage, a pneumococcal sepsis model was used in rats to measure the complex metabolic events that could account for this failure, including the effects of infection on lipolysis and esterification in adipose tissue, fatty acid transport in plasma and the rates of hepatic ketogenesis and whole body oxidation of ketones. Some of the studies were repeated with tularemia as the model infection. From these studies, it was concluded that during pneumococcal sepsis, the failure of rats to become ketonemic during caloric deprivation was the result of reduced ketogenic capacity of the liver and a possibly decreased hepatic supply of fatty acids. The latter appeared to be a secondary consequence of a severe reduction in circulating plasma albumin, the major transport protein for fatty acids, with no effect on the degree of saturation of the albumin with free fatty acids. Also, the infection had no significant effect on the rate of lipolysis or release of fatty acids from adipose tissue. Ketone body usage (oxidation) was either unaffected or reduced during pneumococcal sepsis in rats. Thus, a reduced rate of ketone production in the infected host was primarily responsible for the failure to develop starvation ketonemia under these conditions. The liver of the infected rat host appears to shuttle the fatty acids away from beta-oxidation and ketogenesis and toward triglyceride production, with resulting hepatocellular fatty metamorphosis.
D000214:Acyl Coenzyme A / Q000378:metabolism; D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D005215:Fasting; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005604:Francisella tularensis; D007657:Ketone Bodies / Q000378:metabolism*; D008053:Lipid Mobilization; D008099:Liver / Q000378:metabolism*; D008297:Male; D011008:Pneumococcal Infections / Q000378:metabolism*; D051381:Rats; D018805:Sepsis / Q000378:metabolism*; D012709:Serum Albumin / Q000378:metabolism; D014406:Tularemia / Q000378:metabolism*
D000214:Acyl Coenzyme A; D005230:Fatty Acids, Nonesterified; D007657:Ketone Bodies; D012709:Serum Albumin