AJP - Regulatory, Integrative and Comparative Physiology, Vol 273, Issue 5 1649-R1656, Copyright © 1997 by American Physiological Society
Development of independent ingestive responding to blockade of fatty acid oxidation in rats
S. E. Swithers
Department of Psychological Sciences, Purdue University, West Lafayette, Indiana 47907-1364, USA.
The present studies examined the development of ingestive responsiveness to
blockade of fatty acid oxidation in rat pups using 2-mercaptoacetate (MA),
an inhibitor of mitochondrial acyl-coenzyme A dehydrogenases, or methyl
palmoxirate (MP), an inhibitor of carnitine palmitoyltransferase I (CPT-I).
Rat pups aged 6, 9, 12, or 15 days of age received an intraperitoneal
injection of 0, 100, 200, 400, or 800 mumol/kg MA, and intake of a
commercial half-and-half or 15% glucose diet from the floor of test
containers was assessed in a 30-min test beginning 1 h after administration
of MA. The results demonstrate that, although no dose of MA affected intake
of either diet in pups 9 days or younger, low doses of MA increased intake
and the highest dose suppressed intake of both diets in pups 12 days of age
or older. Physiological measurements indicated that levels of
beta-hydroxybutyrate were significantly lower following doses of 400 or 800
mumol/kg MA in 9-, 12-, and 15-day-old pups and that gastric emptying was
inhibited in 12 and 15 day olds by 800 mumol/kg MA. Intake of a commercial
half-and-half diet from the floor of test containers was also assessed in
12- to 18-day-old rat pups 6.5 h after they received a gavage load of 0,
1.25, 2.5, 5, or 10 mg/kg MP. Unlike MA, MP did not increase intake of a
commercial half-and-half diet in rat pups 12 or 15-18 days of age; instead,
the highest dose of MP suppressed intake in 15- to 18-day-old pups. The
failure of MP to enhance intake in pups at the ages tested is likely
related to composition of dam's milk; rat milk is high in medium-chain
fatty acids that do not require CPT-I for entry into mitochondria. Thus it
is likely that MP does not significantly block fatty acid oxidation in pups
at the ages tested. On the other hand, blockade of fatty acid oxidation
produced by MA significantly affects intake by 12 days of age, suggesting
it may be the first metabolic signal that influences intake in rat pups.
