Jin YJ, Li SZ, Zhao ZS, An JJ, Kim RY, Kim YM, Baik JH, Lim SK.
Carnitine palmitoyltransferase-1 (CPT-1) activity stimulation by
cerulenin via sympathetic nervous system activation overrides
cerulenin's peripheral effect.
Endocrinology. 2004 Jul;145(7):3197-204. Epub 2004 Mar 24.
Division of Endocrinology, Department of Internal Medicine,
College of Medicine, and Brain Korea 21 Project for Medical
Sciences, Yonsei University, Seoul, Korea.
To clarify the paradoxic effects of cerulenin, namely its in
vitro inhibitory effects on fat catabolism and its in vivo
reduction of fat mass, we studied the in vivo and in vitro
effects of cerulenin on carnitine palmitoyltransferase-1 (CPT-1)
activity, the rate-limiting enzyme of fatty acid oxidation. A
single ip injection of cerulenin significantly reduced body
weight and increased core temperature without significantly
reducing food intake. In situ hybridization study revealed that
a single injection of cerulenin did not affect the expression of
orexigenic neuropeptide mRNA. Cerulenin's effect on CPT-1
activity was biphasic in the liver and muscle: early suppression
during the first 1 h and late stimulation in the 3-5 h after ip
treatment. In vitro cerulenin treatment reduced CPT-1 activity,
which was overcome by cotreating with catecholamine.
Intracerebroventricular injection of cerulenin increased CPT-1
activity significantly in soleus muscle, and this effect was
sustained for up to 3 h. Pretreatment with
alpha-methyl-p-tyrosine inhibited the cerulenin-induced increase
in core temperature and the late-phase stimulating effect of
cerulenin on CPT-1 activity. In adrenalectomized mice, cerulenin
also increased the activity. In vivo cerulenin treatment
enhanced muscle CPT-1 activity in monosodium glutamate-treated
arcuate nucleus lesioned mice but not in gold thioglucose-treated
ventromedial hypothalamus lesioned mice. These findings suggest
that cerulenin-induced late-phase stimulating effects on CPT-1
activity and energy expenditure is mediated by the activation of
innervated sympathetic nervous system neurons through the firing
of undefined neurons of the ventromedial hypothalamus, rather
than the arcuate nucleus.
PMID: 15044358
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