PMID- 37824329
OWN - NLM
STAT- MEDLINE
DCOM- 20231106
LR  - 20231113
IS  - 2211-1247 (Electronic)
VI  - 42
IP  - 10
DP  - 2023 Oct 31
TI  - ApoE enhances mitochondrial metabolism via microRNA-142a/146a-regulated circuits 
      that suppress hematopoiesis and inflammation in hyperlipidemia.
PG  - 113206
LID - S2211-1247(23)01218-4 [pii]
LID - 10.1016/j.celrep.2023.113206 [doi]
AB  - Apolipoprotein E (ApoE) is recognized for its pleiotropic properties that 
      suppress inflammation. We report that ApoE serves as a metabolic rheostat that 
      regulates microRNA control of glycolytic and mitochondrial activity in myeloid 
      cells and hematopoietic stem and progenitor cells (HSPCs). ApoE expression in 
      myeloid cells increases microRNA-146a, which reduces nuclear factor kappaB 
      (NF-kappaB)-driven GLUT1 expression and glycolytic activity. In contrast, ApoE 
      expression reduces microRNA-142a, which increases carnitine palmitoyltransferase 
      1a (CPT1A) expression, fatty acid oxidation, and oxidative phosphorylation. 
      Improved mitochondrial metabolism by ApoE expression causes an enrichment of 
      tricarboxylic acid (TCA) cycle metabolites and nicotinamide adenine dinucleotide 
      (NAD(+)) in macrophages. The study of mice with conditional ApoE expression 
      supports the capacity of ApoE to foster microRNA-controlled immunometabolism. 
      Modulation of microRNA-146a and -142a in the hematopoietic system of 
      hyperlipidemic mice using RNA mimics and antagonists, respectively, improves 
      mitochondrial metabolism, which suppresses inflammation and hematopoiesis. Our 
      findings unveil microRNA regulatory circuits, controlled by ApoE, that exert 
      metabolic control over hematopoiesis and inflammation in hyperlipidemia.
CI  - Published by Elsevier Inc.
FAU - Phu, Tuan Anh
AU  - Phu TA
AD  - Department of Veterans Affairs, Surgical Service (112G), San Francisco VA Medical 
      Center, San Francisco, CA 94121, USA; Northern California Institute for Research 
      and Education, San Francisco, CA 94121, USA.
FAU - Vu, Ngan K
AU  - Vu NK
AD  - Department of Veterans Affairs, Surgical Service (112G), San Francisco VA Medical 
      Center, San Francisco, CA 94121, USA; Northern California Institute for Research 
      and Education, San Francisco, CA 94121, USA.
FAU - Ng, Martin
AU  - Ng M
AD  - Department of Veterans Affairs, Surgical Service (112G), San Francisco VA Medical 
      Center, San Francisco, CA 94121, USA; Northern California Institute for Research 
      and Education, San Francisco, CA 94121, USA.
FAU - Gao, Alex S
AU  - Gao AS
AD  - Department of Veterans Affairs, Surgical Service (112G), San Francisco VA Medical 
      Center, San Francisco, CA 94121, USA; Northern California Institute for Research 
      and Education, San Francisco, CA 94121, USA.
FAU - Stoolman, Joshua S
AU  - Stoolman JS
AD  - Department of Medicine, Northwestern University Feinberg School of Medicine, 
      Chicago, IL 60611, USA.
FAU - Chandel, Navdeep S
AU  - Chandel NS
AD  - Department of Medicine, Northwestern University Feinberg School of Medicine, 
      Chicago, IL 60611, USA; Department of Biochemistry & Molecular Genetics, 
      Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
FAU - Raffai, Robert L
AU  - Raffai RL
AD  - Department of Veterans Affairs, Surgical Service (112G), San Francisco VA Medical 
      Center, San Francisco, CA 94121, USA; Northern California Institute for Research 
      and Education, San Francisco, CA 94121, USA; Department of Surgery, Division of 
      Endovascular and Vascular Surgery, University of California, San Francisco, San 
      Francisco, CA 94143, USA. Electronic address: robert.raffai@ucsf.edu.
LA  - eng
GR  - P30 DK063720/DK/NIDDK NIH HHS/United States
GR  - R01 HL133575/HL/NHLBI NIH HHS/United States
GR  - P01 HL154998/HL/NHLBI NIH HHS/United States
GR  - P01 AG049665/AG/NIA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20231011
PL  - United States
TA  - Cell Rep
JT  - Cell reports
JID - 101573691
RN  - 0 (MicroRNAs)
RN  - 0 (Apolipoproteins E)
SB  - IM
MH  - Mice
MH  - Animals
MH  - *Hyperlipidemias/genetics/metabolism
MH  - Inflammation/metabolism
MH  - *MicroRNAs/genetics/metabolism
MH  - *Metabolic Diseases
MH  - Hematopoiesis
MH  - Apolipoproteins E/genetics
OTO - NOTNLM
OT  - ApoE
OT  - CP: Metabolism
OT  - CPT1A
OT  - Glut1
OT  - fatty acid oxidation
OT  - hematopoiesis
OT  - inflammation
OT  - macrophage
OT  - microRNA-142a
OT  - microRNA-146a
OT  - mitochondrial metabolism
COIS- Declaration of interests The authors declare no competing interests.
EDAT- 2023/10/12 18:42
MHDA- 2023/11/06 06:43
CRDT- 2023/10/12 12:35
PHST- 2022/03/21 00:00 [received]
PHST- 2023/05/08 00:00 [revised]
PHST- 2023/09/19 00:00 [accepted]
PHST- 2023/11/06 06:43 [medline]
PHST- 2023/10/12 18:42 [pubmed]
PHST- 2023/10/12 12:35 [entrez]
AID - S2211-1247(23)01218-4 [pii]
AID - 10.1016/j.celrep.2023.113206 [doi]
PST - ppublish
SO  - Cell Rep. 2023 Oct 31;42(10):113206. doi: 10.1016/j.celrep.2023.113206. Epub 2023 
      Oct 11.