PMID- 23651731
OWN - NLM
STAT- MEDLINE
DCOM- 20130923
LR  - 20161126
IS  - 0006-3002 (Print)
IS  - 0006-3002 (Linking)
VI  - 1832
IP  - 10
DP  - 2013 Oct
TI  - Activation of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase during 
      high fat diet feeding.
PG  - 1560-8
LID - S0925-4439(13)00148-8 [pii]
LID - 10.1016/j.bbadis.2013.04.024 [doi]
AB  - The liver plays a central role in regulating cholesterol homeostasis. High fat 
      diets have been shown to induce obesity and hyperlipidemia. Despite considerable 
      advances in our understanding of cholesterol metabolism, the regulation of liver 
      cholesterol biosynthesis in response to high fat diet feeding has not been fully 
      addressed. The aim of the present study was to investigate mechanisms by which a 
      high fat diet caused activation of liver 3-hydroxy-3-methylglutaryl coenzyme A 
      reductase (HMG-CoA reductase) leading to increased cholesterol biosynthesis. Mice 
      were fed a high fat diet (60% kcal fat) for 5weeks. High fat diet feeding induced 
      weight gain and elevated lipid levels (total cholesterol and triglyceride) in 
      both the liver and serum. Despite cholesterol accumulation in the liver, there 
      was a significant increase in hepatic HMG-CoA reductase mRNA and protein 
      expression as well as enzyme activity. The DNA binding activity of sterol 
      regulatory element binding protein (SREBP)-2 and specific protein 1 (Sp1) were 
      also increased in the liver of mice fed a high fat diet. To validate the in vivo 
      findings, HepG2 cells were treated with palmitic acid. Such a treatment activated 
      SREBP-2 as well as increased the mRNA and enzyme activity of HMG-CoA reductase 
      leading to intracellular cholesterol accumulation. Inhibition of Sp1 by siRNA 
      transfection abolished palmitic acid-induced SREBP-2 and HMG-CoA reductase mRNA 
      expression. These results suggest that Sp1-mediated SREBP-2 activation 
      contributes to high fat diet induced HMG-CoA reductase activation and increased 
      cholesterol biosynthesis. This may play a role in liver cholesterol accumulation 
      and hypercholesterolemia.
CI  - Copyright (c) 2013 Elsevier B.V. All rights reserved.
FAU - Wu, Nan
AU  - Wu N
AD  - St. Boniface Hospital Research Centre, Winnipeg, Canada.
FAU - Sarna, Lindsei K
AU  - Sarna LK
FAU - Hwang, Sun-Young
AU  - Hwang SY
FAU - Zhu, Qingjun
AU  - Zhu Q
FAU - Wang, Pengqi
AU  - Wang P
FAU - Siow, Yaw L
AU  - Siow YL
FAU - O, Karmin
AU  - O K
LA  - eng
GR  - Canadian Institutes of Health Research/Canada
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130504
PL  - Netherlands
TA  - Biochim Biophys Acta
JT  - Biochimica et biophysica acta
JID - 0217513
RN  - 0 (DNA Primers)
RN  - 0 (Dietary Fats)
RN  - 0 (Sp1 Transcription Factor)
RN  - 0 (Srebf2 protein, mouse)
RN  - 0 (Sterol Regulatory Element Binding Protein 2)
RN  - EC 1.1.1.- (Hydroxymethylglutaryl CoA Reductases)
SB  - IM
MH  - Animals
MH  - Base Sequence
MH  - Cell Line
MH  - DNA Primers
MH  - Dietary Fats/*administration & dosage
MH  - Enzyme Activation
MH  - Gene Expression Regulation, Enzymologic/physiology
MH  - Humans
MH  - Hydroxymethylglutaryl CoA Reductases/genetics/*metabolism
MH  - Lipid Metabolism
MH  - Liver/metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Real-Time Polymerase Chain Reaction
MH  - Sp1 Transcription Factor/physiology
MH  - Sterol Regulatory Element Binding Protein 2/physiology
OTO - NOTNLM
OT  - Cholesterol
OT  - Fatty liver
OT  - HMG-CoA reductase
OT  - SREBP-2
EDAT- 2013/05/09 06:00
MHDA- 2013/09/24 06:00
CRDT- 2013/05/09 06:00
PHST- 2013/03/20 00:00 [received]
PHST- 2013/04/23 00:00 [revised]
PHST- 2013/04/24 00:00 [accepted]
PHST- 2013/05/09 06:00 [entrez]
PHST- 2013/05/09 06:00 [pubmed]
PHST- 2013/09/24 06:00 [medline]
AID - S0925-4439(13)00148-8 [pii]
AID - 10.1016/j.bbadis.2013.04.024 [doi]
PST - ppublish
SO  - Biochim Biophys Acta. 2013 Oct;1832(10):1560-8. doi: 
      10.1016/j.bbadis.2013.04.024. Epub 2013 May 4.