PMID- 16705061
OWN - NLM
STAT- MEDLINE
DCOM- 20061024
LR  - 20200128
IS  - 0193-1849 (Print)
IS  - 0193-1849 (Linking)
VI  - 291
IP  - 4
DP  - 2006 Oct
TI  - Overexpression of acyl-CoA synthetase-1 increases lipid deposition in hepatic 
      (HepG2) cells and rodent liver in vivo.
PG  - E737-44
AB  - Accumulation of intracellular lipid in obesity is associated with metabolic 
      disease in many tissues including liver. Storage of fatty acid as triglyceride 
      (TG) requires the activation of fatty acids to long-chain acyl-CoAs (LC-CoA) by 
      the enzyme acyl-CoA synthetase (ACSL). There are five known isoforms of ACSL 
      (ACSL1, -3, -4, -5, -6), which vary in their tissue specificity and affinity for 
      fatty acid substrates. To investigate the role of ACSL1 in the regulation of 
      lipid metabolism, we used adenoviral-mediated gene transfer to overexpress ACSL1 
      in the human hepatoma cell-line HepG2 and in liver of rodents. Infection of HepG2 
      cells with the adenoviral construct AdACSL1 increased ACSL activity >10-fold 
      compared with controls after 24 h. HepG2 cells overexpressing ACSL1 had a 40% 
      higher triglyceride (TG) content (93 +/- 3 vs. 67 +/- 2 nmol/mg protein in 
      controls, P < 0.05) after 24-h exposure to 1 mM oleate. Furthermore, ACSL1 
      overexpression produced a 60% increase in cellular LCA-CoA content (160 +/- 6 vs. 
      100 +/- 6 nmol/g protein in controls, P < 0.05) and increased [(14)C]oleate 
      incorporation into TG without significantly altering fatty acid oxidation. In 
      mice, AdACSL1 administration increased ACSL1 mRNA and protein more than fivefold 
      over controls at 4 days postinfection. ACSL1 overexpression caused a twofold 
      increase in TG content in mouse liver (39 +/- 4 vs. 20 +/- 2 mumol/g wet wt in 
      controls, P < 0.05), and overexpression in rat liver increased [1-(14)C]palmitate 
      clearance into liver TG. These in vitro and in vivo results suggest a pivotal 
      role for ACSL1 in regulating TG synthesis in liver.
FAU - Parkes, Heidi A
AU  - Parkes HA
AD  - Diabetes and Obesity Research Program, Garvan Institute of Medical Research, 384 
      Victoria St. Darlinghurst, New South Wales, 2010, Australia.
FAU - Preston, Elaine
AU  - Preston E
FAU - Wilks, Donna
AU  - Wilks D
FAU - Ballesteros, Mercedes
AU  - Ballesteros M
FAU - Carpenter, Lee
AU  - Carpenter L
FAU - Wood, Leonie
AU  - Wood L
FAU - Kraegen, Edward W
AU  - Kraegen EW
FAU - Furler, Stuart M
AU  - Furler SM
FAU - Cooney, Gregory J
AU  - Cooney GJ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20060516
PL  - United States
TA  - Am J Physiol Endocrinol Metab
JT  - American journal of physiology. Endocrinology and metabolism
JID - 100901226
RN  - 0 (Fatty Acids, Nonesterified)
RN  - 0 (Triglycerides)
RN  - 147336-22-9 (Green Fluorescent Proteins)
RN  - 2UMI9U37CP (Oleic Acid)
RN  - 63231-63-0 (RNA)
RN  - EC 6.2.1.- (Coenzyme A Ligases)
RN  - EC 6.2.1.3 (Acsl1 protein, rat)
SB  - IM
MH  - Adenoviridae/genetics
MH  - Animals
MH  - Cell Line, Tumor
MH  - Coenzyme A Ligases/*biosynthesis/blood/genetics/metabolism
MH  - Eating
MH  - Fatty Acids, Nonesterified/blood/metabolism
MH  - Green Fluorescent Proteins/biosynthesis/genetics
MH  - Immunoblotting
MH  - Lipid Metabolism/*physiology
MH  - Liver/anatomy & histology/enzymology/*metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Obesity/enzymology/*metabolism
MH  - Oleic Acid/genetics/metabolism
MH  - Organ Size
MH  - RNA/chemistry/genetics
MH  - Rats
MH  - Rats, Wistar
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Triglycerides/blood
EDAT- 2006/05/18 09:00
MHDA- 2006/10/25 09:00
CRDT- 2006/05/18 09:00
PHST- 2006/05/18 09:00 [pubmed]
PHST- 2006/10/25 09:00 [medline]
PHST- 2006/05/18 09:00 [entrez]
AID - 00112.2006 [pii]
AID - 10.1152/ajpendo.00112.2006 [doi]
PST - ppublish
SO  - Am J Physiol Endocrinol Metab. 2006 Oct;291(4):E737-44. doi: 
      10.1152/ajpendo.00112.2006. Epub 2006 May 16.