PMID- 22156303
OWN - NLM
STAT- MEDLINE
DCOM- 20121017
LR  - 20240323
IS  - 1943-4456 (Electronic)
IS  - 0091-7451 (Print)
IS  - 0091-7451 (Linking)
VI  - 76
DP  - 2011
TI  - MicroRNAs in metabolism and metabolic diseases.
PG  - 225-33
LID - 10.1101/sqb.2011.76.011049 [doi]
AB  - Aberrant cholesterol/lipid homeostasis is linked to a number of diseases 
      prevalent in the developed world, including metabolic syndrome, type II diabetes, 
      and cardiovascular disease. We have previously uncovered gene regulatory 
      mechanisms of the sterol regulatory element-binding protein (SREBP) family of 
      transcription factors, which control the expression of genes involved in 
      cholesterol and lipid biosynthesis and uptake. Intriguingly, we recently 
      discovered conserved microRNAs (miR-33a/b) embedded within intronic sequences of 
      the human SREBF genes that act in a concerted manner with their host gene 
      products to regulate cholesterol/lipid homeostasis. Indeed, miR-33a/b control the 
      levels of ATP-binding cassette (ABC) transporter ABCA1, a cholesterol efflux pump 
      critical for high-density lipoprotein (HDL) synthesis and reverse cholesterol 
      transport from peripheral tissues. Importantly, antisense inhibition of miR-33 in 
      mice results in elevated HDL and decreased atherosclerosis. Interestingly, 
      miR-33a/b also act in the fatty acid/lipid homeostasis pathway by controlling the 
      fatty acid beta-oxidation genes carnitine O-octanoyltransferase (CROT), 
      hydroxyacyl-coenzyme A-dehydrogenase (HADHB), and carnitine palmitoyltransferase 
      1A (CPT1A), as well as the energy sensor AMP-activated protein kinase (AMPKalpha1), 
      the NAD(+)-dependent sirtuin SIRT6, and the insulin signaling intermediate IRS2, 
      key regulators of glucose and lipid metabolism. These results have revealed a 
      highly integrated microRNA (miRNA)-host gene circuit governing cholesterol/lipid 
      metabolism and energy homeostasis in mammals that may have important therapeutic 
      implications for the treatment of cardiometabolic disorders.
FAU - Rottiers, V
AU  - Rottiers V
AD  - Massachusetts General Hospital Cancer Center, Charlestown, Massachusetts 02129, 
      USA.
FAU - Najafi-Shoushtari, S H
AU  - Najafi-Shoushtari SH
FAU - Kristo, F
AU  - Kristo F
FAU - Gurumurthy, S
AU  - Gurumurthy S
FAU - Zhong, L
AU  - Zhong L
FAU - Li, Y
AU  - Li Y
FAU - Cohen, D E
AU  - Cohen DE
FAU - Gerszten, R E
AU  - Gerszten RE
FAU - Bardeesy, N
AU  - Bardeesy N
FAU - Mostoslavsky, R
AU  - Mostoslavsky R
FAU - Naar, A M
AU  - Naar AM
LA  - eng
GR  - 1R01GM071449/GM/NIGMS NIH HHS/United States
GR  - R01 GM071449/GM/NIGMS NIH HHS/United States
GR  - R01 DK094184/DK/NIDDK NIH HHS/United States
GR  - R21 DK084459/DK/NIDDK NIH HHS/United States
GR  - 1R21DK084459/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20111212
PL  - United States
TA  - Cold Spring Harb Symp Quant Biol
JT  - Cold Spring Harbor symposia on quantitative biology
JID - 1256107
RN  - 0 (ABCA1 protein, human)
RN  - 0 (ATP Binding Cassette Transporter 1)
RN  - 0 (ATP-Binding Cassette Transporters)
RN  - 0 (Fatty Acids)
RN  - 0 (Insulin Receptor Substrate Proteins)
RN  - 0 (MicroRNAs)
RN  - 0 (Sterol Regulatory Element Binding Proteins)
RN  - 97C5T2UQ7J (Cholesterol)
RN  - EC 2.7.11.31 (AMP-Activated Protein Kinases)
RN  - EC 3.5.1.- (Sirtuins)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - AMP-Activated Protein Kinases/metabolism
MH  - ATP Binding Cassette Transporter 1
MH  - ATP-Binding Cassette Transporters/metabolism
MH  - Animals
MH  - Base Sequence
MH  - Biological Transport/genetics
MH  - Cholesterol/metabolism
MH  - Conserved Sequence/genetics
MH  - Energy Metabolism/genetics
MH  - Fatty Acids/metabolism
MH  - Glucose/metabolism
MH  - Homeostasis/genetics
MH  - Humans
MH  - Insulin Receptor Substrate Proteins/metabolism
MH  - Introns/genetics
MH  - Metabolic Diseases/*genetics
MH  - Metabolism/*genetics
MH  - Mice
MH  - MicroRNAs/biosynthesis/genetics/*metabolism
MH  - Models, Biological
MH  - Molecular Sequence Data
MH  - Oxidation-Reduction
MH  - Sirtuins/metabolism
MH  - Sterol Regulatory Element Binding Proteins/genetics/metabolism
PMC - PMC3880782
MID - NIHMS527283
EDAT- 2011/12/14 06:00
MHDA- 2012/10/18 06:00
PMCR- 2014/01/05
CRDT- 2011/12/14 06:00
PHST- 2011/12/14 06:00 [entrez]
PHST- 2011/12/14 06:00 [pubmed]
PHST- 2012/10/18 06:00 [medline]
PHST- 2014/01/05 00:00 [pmc-release]
AID - sqb.2011.76.011049 [pii]
AID - 10.1101/sqb.2011.76.011049 [doi]
PST - ppublish
SO  - Cold Spring Harb Symp Quant Biol. 2011;76:225-33. doi: 
      10.1101/sqb.2011.76.011049. Epub 2011 Dec 12.