PMID- 16219771
OWN - NLM
STAT- MEDLINE
DCOM- 20060203
LR  - 20210209
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 280
IP  - 48
DP  - 2005 Dec 2
TI  - A role for hypothalamic malonyl-CoA in the control of food intake.
PG  - 39681-3
AB  - The cellular level of malonyl-CoA, an intermediate in fatty acid biosynthesis, 
      depends on its rate of synthesis catalyzed by acetyl-CoA carboxylase relative to 
      its rate of utilization and degradation catalyzed by fatty acid synthase and 
      malonyl-CoA decarboxylase, respectively. Recent evidence suggests that 
      hypothalamic malonyl-CoA functions in the regulation of feeding behavior by 
      altering the expression of key orexigenic and anorexigenic neuropeptides. Here we 
      report that 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR), a 5'-AMP 
      kinase activator, rapidly lowers malonyl-CoA both in GT1-7 hypothalamic neurons 
      and in the hypothalami of mice. These effects correlate closely with the 
      phosphorylation of acetyl-CoA carboxylase, an established target of AMP kinase. 
      Intracerebroventricular (i.c.v.) administration of AICAR rapidly lowers 
      hypothalamic [malonyl-CoA] and increases food intake. Expression of an adenoviral 
      cytosolic malonyl-CoA decarboxylase vector (Ad-cMCD) in hypothalamic GT1-7 cells 
      decreases malonyl-CoA. When delivered by bilateral stereotaxic injection into the 
      ventral hypothalamus (encompassing the arcuate nucleus) of mice, Ad-cMCD 
      increases food intake and body weight. Ad-MCD delivered into the ventral 
      hypothalamus also reverses the rapid suppression of food intake caused by 
      i.c.v.-administered C75, a fatty acid synthase inhibitor that increases 
      hypothalamic [malonyl-CoA]. Taken together these findings implicate malonyl-CoA 
      in the hypothalamic regulation of feeding behavior.
FAU - Hu, Zhiyuan
AU  - Hu Z
AD  - Department of Biological Chemistry, Johns Hopkins University School of Medicine, 
      Baltimore, Maryland 21205, USA.
FAU - Dai, Yun
AU  - Dai Y
FAU - Prentki, Marc
AU  - Prentki M
FAU - Chohnan, Shigeru
AU  - Chohnan S
FAU - Lane, M Daniel
AU  - Lane MD
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20051011
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (DNA, Complementary)
RN  - 0 (Fatty Acids)
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (Peptides)
RN  - 0 (Ribonucleotides)
RN  - 360-97-4 (Aminoimidazole Carboxamide)
RN  - 524-14-1 (Malonyl Coenzyme A)
RN  - EC 2.3.1.85 (Fatty Acid Synthases)
RN  - EC 2.7.4.3 (Adenylate Kinase)
RN  - EC 4.1.1.- (Carboxy-Lyases)
RN  - EC 4.1.1.9 (malonyl-CoA decarboxylase)
RN  - F0X88YW0YK (AICA ribonucleotide)
SB  - IM
MH  - Adenoviridae/genetics
MH  - Adenylate Kinase/metabolism
MH  - Aminoimidazole Carboxamide/analogs & derivatives/chemistry
MH  - Animals
MH  - Carboxy-Lyases/metabolism
MH  - Catalysis
MH  - Cells, Cultured
MH  - Cytosol/enzymology/metabolism
MH  - DNA, Complementary/metabolism
MH  - Electrophoresis, Polyacrylamide Gel
MH  - Fatty Acid Synthases/metabolism
MH  - Fatty Acids/metabolism
MH  - *Feeding Behavior
MH  - Genetic Vectors
MH  - Hypoglycemic Agents/pharmacology
MH  - Hypothalamus/cytology/metabolism/pathology
MH  - Lac Operon
MH  - Male
MH  - Malonyl Coenzyme A/metabolism/*physiology
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Neurons/metabolism
MH  - Peptides/chemistry
MH  - Phosphorylation
MH  - Rats
MH  - Ribonucleotides/chemistry
MH  - Time Factors
EDAT- 2005/10/13 09:00
MHDA- 2006/02/04 09:00
CRDT- 2005/10/13 09:00
PHST- 2005/10/13 09:00 [pubmed]
PHST- 2006/02/04 09:00 [medline]
PHST- 2005/10/13 09:00 [entrez]
AID - S0021-9258(19)48093-9 [pii]
AID - 10.1074/jbc.C500398200 [doi]
PST - ppublish
SO  - J Biol Chem. 2005 Dec 2;280(48):39681-3. doi: 10.1074/jbc.C500398200. Epub 2005 
      Oct 11.