PMID- 24760992
OWN - NLM
STAT- MEDLINE
DCOM- 20140820
LR  - 20171116
IS  - 1522-1555 (Electronic)
IS  - 0193-1849 (Linking)
VI  - 306
IP  - 12
DP  - 2014 Jun 15
TI  - Mice lacking NOX2 are hyperphagic and store fat preferentially in the liver.
PG  - E1341-53
LID - 10.1152/ajpendo.00089.2014 [doi]
AB  - Chronic low-grade inflammation is an important contributor to the development of 
      insulin resistance, a hallmark of type 2 diabetes mellitus (T2DM). Obesity and 
      high-fat feeding lead to infiltration of immune cells into metabolic tissues, 
      promoting inflammation and insulin resistance. We hypothesized that macrophages 
      from mice lacking NOX2 (Cybb), an essential component of the NADPH oxidase 
      complex highly expressed in immune cells and associated with their inflammatory 
      response, would be less inflammatory and that these mice would be protected from 
      the development of high-fat-induced insulin resistance. Bone marrow-derived 
      macrophages from NOX2 knockout (NOX2-KO) mice expressed lower levels of 
      inflammatory markers (Nos2, Il6); however, NOX2-KO mice were hyperphagic and 
      gained more weight than wild-type (WT) mice when fed either a chow or a high-fat 
      (HF) diet. Surprisingly, NOX2-KO mice stored less lipid in epididymal white 
      adipose tissue but more lipid in liver and had higher indexes of liver 
      inflammation and macrophage infiltration than WT mice. Contrary to our 
      hypothesis, HF-fed NOX2-KO mice were hyperinsulinemic and more insulin resistant 
      than HF-fed WT mice, likely as a result of their higher hepatic steatosis and 
      inflammation. In summary, NOX2 depletion promoted hyperphagia, hepatic steatosis, 
      and inflammation with either normal or high-fat feeding, exacerbating insulin 
      resistance. We propose that NOX2 participates in food intake control and lipid 
      distribution in mice.
CI  - Copyright (c) 2014 the American Physiological Society.
FAU - Costford, Sheila R
AU  - Costford SR
AD  - The Hospital for Sick Children, Toronto, Ontario, Canada;
FAU - Castro-Alves, Jason
AU  - Castro-Alves J
AD  - The Hospital for Sick Children, Toronto, Ontario, Canada; University of Toronto, 
      Toronto, Ontario, Canada.
FAU - Chan, Kenny L
AU  - Chan KL
AD  - The Hospital for Sick Children, Toronto, Ontario, Canada; University of Toronto, 
      Toronto, Ontario, Canada.
FAU - Bailey, Liane J
AU  - Bailey LJ
AD  - The Hospital for Sick Children, Toronto, Ontario, Canada; University of Toronto, 
      Toronto, Ontario, Canada.
FAU - Woo, Minna
AU  - Woo M
AD  - Toronto General Research Institute, University Health Network, Toronto, Ontario, 
      Canada; University of Toronto, Toronto, Ontario, Canada.
FAU - Belsham, Denise D
AU  - Belsham DD
AD  - University of Toronto, Toronto, Ontario, Canada.
FAU - Brumell, John H
AU  - Brumell JH
AD  - The Hospital for Sick Children, Toronto, Ontario, Canada; University of Toronto, 
      Toronto, Ontario, Canada.
FAU - Klip, Amira
AU  - Klip A
AD  - The Hospital for Sick Children, Toronto, Ontario, Canada; University of Toronto, 
      Toronto, Ontario, Canada amira@sickkids.ca.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140422
PL  - United States
TA  - Am J Physiol Endocrinol Metab
JT  - American journal of physiology. Endocrinology and metabolism
JID - 100901226
RN  - 0 (Membrane Glycoproteins)
RN  - EC 1.6.3.- (Cybb protein, mouse)
RN  - EC 1.6.3.- (NADPH Oxidase 2)
RN  - EC 1.6.3.- (NADPH Oxidases)
SB  - IM
MH  - Adipose Tissue, White/immunology/metabolism/pathology
MH  - Animals
MH  - *Appetite Regulation
MH  - Appetitive Behavior
MH  - Behavior, Animal
MH  - Cells, Cultured
MH  - Diabetes Mellitus, Type 2/complications/etiology
MH  - Diet, High-Fat/adverse effects
MH  - Fatty Liver/complications/*etiology
MH  - Hyperphagia/immunology/*metabolism/pathology/physiopathology
MH  - *Insulin Resistance
MH  - *Lipid Metabolism
MH  - Liver/immunology/*metabolism/pathology
MH  - Macrophages/immunology/metabolism/pathology
MH  - Male
MH  - Membrane Glycoproteins/genetics/*metabolism
MH  - Mice
MH  - Mice, 129 Strain
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - NADPH Oxidase 2
MH  - NADPH Oxidases/genetics/*metabolism
MH  - Non-alcoholic Fatty Liver Disease
MH  - Obesity/complications/etiology
OTO - NOTNLM
OT  - NOX2
OT  - fatty liver
OT  - hyperphagia
OT  - insulin resistance
EDAT- 2014/04/25 06:00
MHDA- 2014/08/21 06:00
CRDT- 2014/04/25 06:00
PHST- 2014/04/25 06:00 [entrez]
PHST- 2014/04/25 06:00 [pubmed]
PHST- 2014/08/21 06:00 [medline]
AID - ajpendo.00089.2014 [pii]
AID - 10.1152/ajpendo.00089.2014 [doi]
PST - ppublish
SO  - Am J Physiol Endocrinol Metab. 2014 Jun 15;306(12):E1341-53. doi: 
      10.1152/ajpendo.00089.2014. Epub 2014 Apr 22.