PMID- 26847458
OWN - NLM
STAT- MEDLINE
DCOM- 20161213
LR  - 20240213
IS  - 1432-1440 (Electronic)
IS  - 0946-2716 (Print)
IS  - 0946-2716 (Linking)
VI  - 94
IP  - 3
DP  - 2016 Mar
TI  - Emerging evidence for beneficial macrophage functions in atherosclerosis and 
      obesity-induced insulin resistance.
PG  - 267-75
LID - 10.1007/s00109-016-1385-4 [doi]
AB  - The discovery that obesity promotes macrophage accumulation in visceral fat led 
      to the emergence of a new field of inquiry termed "immunometabolism". This broad 
      field of study was founded on the premise that inflammation and the corresponding 
      increase in macrophage number and activity was a pathologic feature of metabolic 
      diseases. There is abundant data in both animal and human studies that supports 
      this assertation. Established adverse effects of inflammation in visceral fat 
      include decreased glucose and fatty acid uptake, inhibition of insulin signaling, 
      and ectopic triglyceride accumulation. Likewise, in the atherosclerotic plaque, 
      macrophage accumulation and activation results in plaque expansion and 
      destabilization. Despite these facts, there is an accumulating body of evidence 
      that macrophages also have beneficial functions in both atherosclerosis and 
      visceral obesity. Potentially beneficial functions that are common to these 
      different contexts include the regulation of efferocytosis, lipid buffering, and 
      anti-inflammatory effects. Autophagy, the process by which cytoplasmic contents 
      are delivered to the lysosome for degradation, is integral to many of these 
      protective biologic functions. The macrophage utilizes autophagy as a molecular 
      tool to maintain tissue integrity and homeostasis at baseline (e.g., bone growth) 
      and in the face of ongoing metabolic insults (e.g., fasting, 
      hypercholesterolemia, obesity). Herein, we highlight recent evidence 
      demonstrating that abrogation of certain macrophage functions, in particular 
      autophagy, exacerbates both atherosclerosis and obesity-induced insulin 
      resistance. Insulin signaling through mammalian target of rapamycin (mTOR) is a 
      crucial regulatory node that links nutrient availability to macrophage autophagic 
      flux. A more precise understanding of the metabolic substrates and triggers for 
      macrophage autophagy may allow therapeutic manipulation of this pathway. These 
      observations underscore the complexity of the field "immunometabolism", validate 
      its importance, and raise many fascinating and important questions for future 
      study.
FAU - Fitzgibbons, Timothy P
AU  - Fitzgibbons TP
AD  - Cardiovascular Division, Department of Medicine, University of Massachusetts 
      Medical School, 55 Lake Avenue North, Worcester, MA, 01655, USA. 
      timothy.fitzgibbons@umassmed.edu.
FAU - Czech, Michael P
AU  - Czech MP
AD  - Program in Molecular Medicine, University of Massachusetts Medical School, 
      Worcester, MA, 01655, USA.
LA  - eng
GR  - R01 DK030898/DK/NIDDK NIH HHS/United States
GR  - R37 DK030898/DK/NIDDK NIH HHS/United States
GR  - DK030898/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20160204
PL  - Germany
TA  - J Mol Med (Berl)
JT  - Journal of molecular medicine (Berlin, Germany)
JID - 9504370
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Adipose Tissue/immunology/metabolism/pathology
MH  - Animals
MH  - Atherosclerosis/*complications/immunology/metabolism/pathology
MH  - Autophagy
MH  - Humans
MH  - Inflammation/complications/immunology/metabolism/pathology
MH  - *Insulin Resistance/immunology
MH  - Lipid Metabolism
MH  - Macrophages/*immunology/metabolism/pathology
MH  - Obesity/*complications/immunology/metabolism/pathology
MH  - TOR Serine-Threonine Kinases/immunology/metabolism
MH  - Thermogenesis
PMC - PMC4803808
OTO - NOTNLM
OT  - Atherosclerosis
OT  - Autophagy
OT  - Cholesterol
OT  - Insulin resistance
OT  - Macrophage
OT  - Visceral adipose
OT  - mTOR
EDAT- 2016/02/06 06:00
MHDA- 2016/12/15 06:00
PMCR- 2016/02/04
CRDT- 2016/02/06 06:00
PHST- 2015/11/12 00:00 [received]
PHST- 2016/01/19 00:00 [accepted]
PHST- 2016/01/14 00:00 [revised]
PHST- 2016/02/06 06:00 [entrez]
PHST- 2016/02/06 06:00 [pubmed]
PHST- 2016/12/15 06:00 [medline]
PHST- 2016/02/04 00:00 [pmc-release]
AID - 10.1007/s00109-016-1385-4 [pii]
AID - 1385 [pii]
AID - 10.1007/s00109-016-1385-4 [doi]
PST - ppublish
SO  - J Mol Med (Berl). 2016 Mar;94(3):267-75. doi: 10.1007/s00109-016-1385-4. Epub 
      2016 Feb 4.