AJP - Endocrinology and Metabolism, Vol 247, Issue 2 173-E180, Copyright © 1984 by American Physiological Society
Mechanisms of catecholamine effects on ketogenesis
M. Bahnsen, J. M. Burrin, D. G. Johnston, A. Pernet, M. Walker and K. G. Alberti
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.
