Mechanisms of catecholamine effects on ketogenesis.
Ketogenesis may be controlled at several sites. Lipolysis with release of plasma nonesterified fatty acid (NEFA) substrate is the first step. Plasma NEFA are taken up by the liver in a concentration-dependent fashion and, after conversion to the acyl-CoA derivative, may either be reesterified or enter the mitochondria via the carnitine shuttle. After beta-oxidation the resultant acetyl-CoA may either be converted to ketone bodies that are then released into the circulation or be condensed with oxaloacetate and enter the tricarboxylic acid cycle, the third potential control point. In humans, infusion of epinephrine causes a transient two- to threefold increase in fatty acids, glycerol, and ketone bodies. Insulin levels show a small absolute increase. Norepinephrine has similar effects, although insulin levels tend to be suppressed and glucagon levels rise somewhat. If somatostatin is added simultaneously, the lipolytic and ketogenic effects are accentuated and prolonged. Dopamine, in a high dose, has no effect on ketone bodies alone but shows small increases in NEFA and ketone bodies in the presence of somatostatin and may play a modulatory role in ketogenesis. The ketogenic effect of catecholamines could thus be in the adipocyte or in the liver. Studies with perfused liver or hepatocytes showed only trivial effects on ketogenesis even with supraphysiological doses of catecholamines. Furthermore infusion studies in rats showed decreased rather than increased ketogenesis with no change in NEFA levels. The data suggest that a) there are species differences, and b) in humans epinephrine- and norepinephrine-induced increases in ketogenesis are secondary to increases in NEFA substrate supply.
D000818:Animals; D004285:Dogs; D004298:Dopamine; D004837:Epinephrine / Q000494:pharmacology; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005990:Glycerol / Q000097:blood; D006801:Humans; D007657:Ketone Bodies / Q000378:metabolism*; D007700:Kinetics; D008055:Lipids / Q000097:blood*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D009638:Norepinephrine / Q000494:pharmacology; D013004:Somatostatin
D005230:Fatty Acids, Nonesterified; D007657:Ketone Bodies; D008055:Lipids; D013004:Somatostatin; D005990:Glycerol; D004298:Dopamine; D009638:Norepinephrine; D004837:Epinephrine