PMID- 23533380
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20130328
LR  - 20211021
IS  - 1687-4757 (Print)
IS  - 1687-4765 (Electronic)
VI  - 2013
DP  - 2013
TI  - Inhibitors of Fatty Acid Synthesis Induce PPAR alpha -Regulated Fatty Acid beta 
      -Oxidative Genes: Synergistic Roles of L-FABP and Glucose.
PG  - 865604
LID - 10.1155/2013/865604 [doi]
LID - 865604
AB  - While TOFA (acetyl CoA carboxylase inhibitor) and C75 (fatty acid synthase 
      inhibitor) prevent lipid accumulation by inhibiting fatty acid synthesis, the 
      mechanism of action is not simply accounted for by inhibition of the enzymes 
      alone. Liver fatty acid binding protein (L-FABP), a mediator of long chain fatty 
      acid signaling to peroxisome proliferator-activated receptor- alpha (PPAR alpha ) in the 
      nucleus, was found to bind TOFA and its activated CoA thioester, TOFyl-CoA, with 
      high affinity while binding C75 and C75-CoA with lower affinity. Binding of TOFA 
      and C75-CoA significantly altered L-FABP secondary structure. High (20 mM) but 
      not physiological (6 mM) glucose conferred on both TOFA and C75 the ability to 
      induce PPAR alpha transcription of the fatty acid beta -oxidative enzymes CPT1A, CPT2, 
      and ACOX1 in cultured primary hepatocytes from wild-type (WT) mice. However, 
      L-FABP gene ablation abolished the effects of TOFA and C75 in the context of high 
      glucose. These effects were not associated with an increased cellular level of 
      unesterified fatty acids but rather by increased intracellular glucose. These 
      findings suggested that L-FABP may function as an intracellular fatty acid 
      synthesis inhibitor binding protein facilitating TOFA and C75-mediated induction 
      of PPAR alpha in the context of high glucose at levels similar to those in 
      uncontrolled diabetes.
FAU - Huang, Huan
AU  - Huang H
AD  - Department of Physiology and Pharmacology, Texas A&M University, TAMU 4466, 
      College Station, TX 77843-4466, USA.
FAU - McIntosh, Avery L
AU  - McIntosh AL
FAU - Martin, Gregory G
AU  - Martin GG
FAU - Petrescu, Anca D
AU  - Petrescu AD
FAU - Landrock, Kerstin K
AU  - Landrock KK
FAU - Landrock, Danilo
AU  - Landrock D
FAU - Kier, Ann B
AU  - Kier AB
FAU - Schroeder, Friedhelm
AU  - Schroeder F
LA  - eng
GR  - R01 DK041402/DK/NIDDK NIH HHS/United States
PT  - Journal Article
DEP - 20130226
PL  - United States
TA  - PPAR Res
JT  - PPAR research
JID - 101269101
PMC - PMC3600304
EDAT- 2013/03/28 06:00
MHDA- 2013/03/28 06:01
PMCR- 2013/02/26
CRDT- 2013/03/28 06:00
PHST- 2012/11/13 00:00 [received]
PHST- 2012/12/21 00:00 [accepted]
PHST- 2013/03/28 06:00 [entrez]
PHST- 2013/03/28 06:00 [pubmed]
PHST- 2013/03/28 06:01 [medline]
PHST- 2013/02/26 00:00 [pmc-release]
AID - 10.1155/2013/865604 [doi]
PST - ppublish
SO  - PPAR Res. 2013;2013:865604. doi: 10.1155/2013/865604. Epub 2013 Feb 26.