PMID- 29528335
OWN - NLM
STAT- MEDLINE
DCOM- 20190910
LR  - 20190910
IS  - 1558-8238 (Electronic)
IS  - 0021-9738 (Print)
IS  - 0021-9738 (Linking)
VI  - 128
IP  - 4
DP  - 2018 Apr 2
TI  - Insulin resistance causes inflammation in adipose tissue.
PG  - 1538-1550
LID - 96139 [pii]
LID - 10.1172/JCI96139 [doi]
AB  - Obesity is a major risk factor for insulin resistance and type 2 diabetes. In 
      adipose tissue, obesity-mediated insulin resistance correlates with the 
      accumulation of proinflammatory macrophages and inflammation. However, the causal 
      relationship of these events is unclear. Here, we report that obesity-induced 
      insulin resistance in mice precedes macrophage accumulation and inflammation in 
      adipose tissue. Using a mouse model that combines genetically induced, 
      adipose-specific insulin resistance (mTORC2-knockout) and diet-induced obesity, 
      we found that insulin resistance causes local accumulation of proinflammatory 
      macrophages. Mechanistically, insulin resistance in adipocytes results in 
      production of the chemokine monocyte chemoattractant protein 1 (MCP1), which 
      recruits monocytes and activates proinflammatory macrophages. Finally, insulin 
      resistance (high homeostatic model assessment of insulin resistance [HOMA-IR]) 
      correlated with reduced insulin/mTORC2 signaling and elevated MCP1 production in 
      visceral adipose tissue from obese human subjects. Our findings suggest that 
      insulin resistance in adipose tissue leads to inflammation rather than vice 
      versa.
FAU - Shimobayashi, Mitsugu
AU  - Shimobayashi M
AD  - Biozentrum, University of Basel, Basel, Switzerland.
FAU - Albert, Verena
AU  - Albert V
AD  - Biozentrum, University of Basel, Basel, Switzerland.
FAU - Woelnerhanssen, Bettina
AU  - Woelnerhanssen B
AD  - Department of Research and.
FAU - Frei, Irina C
AU  - Frei IC
AD  - Biozentrum, University of Basel, Basel, Switzerland.
FAU - Weissenberger, Diana
AU  - Weissenberger D
AD  - Biozentrum, University of Basel, Basel, Switzerland.
FAU - Meyer-Gerspach, Anne Christin
AU  - Meyer-Gerspach AC
AD  - Department of Research and.
FAU - Clement, Nicolas
AU  - Clement N
AD  - Department of Surgery, St. Claraspital, Basel, Switzerland.
FAU - Moes, Suzette
AU  - Moes S
AD  - Biozentrum, University of Basel, Basel, Switzerland.
FAU - Colombi, Marco
AU  - Colombi M
AD  - Biozentrum, University of Basel, Basel, Switzerland.
FAU - Meier, Jerome A
AU  - Meier JA
AD  - Biozentrum, University of Basel, Basel, Switzerland.
FAU - Swierczynska, Marta M
AU  - Swierczynska MM
AD  - Biozentrum, University of Basel, Basel, Switzerland.
FAU - Jeno, Paul
AU  - Jeno P
AD  - Biozentrum, University of Basel, Basel, Switzerland.
FAU - Beglinger, Christoph
AU  - Beglinger C
AD  - Department of Research and.
FAU - Peterli, Ralph
AU  - Peterli R
AD  - Department of Surgery, St. Claraspital, Basel, Switzerland.
FAU - Hall, Michael N
AU  - Hall MN
AD  - Biozentrum, University of Basel, Basel, Switzerland.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180312
PL  - United States
TA  - J Clin Invest
JT  - The Journal of clinical investigation
JID - 7802877
RN  - 0 (Ccl2 protein, mouse)
RN  - 0 (Chemokine CCL2)
RN  - EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 2)
SB  - IM
MH  - 3T3-L1 Cells
MH  - Animals
MH  - Chemokine CCL2/genetics/metabolism
MH  - Diabetes Mellitus, Type 2/genetics/metabolism/pathology
MH  - Humans
MH  - Inflammation/genetics/metabolism/pathology
MH  - *Insulin Resistance
MH  - Intra-Abdominal Fat/*metabolism/pathology
MH  - Macrophages/*metabolism/pathology
MH  - Mechanistic Target of Rapamycin Complex 2/genetics/metabolism
MH  - Mice
MH  - Mice, Knockout
MH  - Obesity/genetics/*metabolism/pathology
MH  - Panniculitis/genetics/*metabolism/pathology
MH  - *Signal Transduction
PMC - PMC5873875
OTO - NOTNLM
OT  - Adipose tissue
OT  - Inflammation
OT  - Macrophages
OT  - Metabolism
OT  - Obesity
COIS- Conflict of interest: The authors have declared that no conflict of interest 
      exists.
EDAT- 2018/03/13 06:00
MHDA- 2019/09/11 06:00
PMCR- 2018/07/02
CRDT- 2018/03/13 06:00
PHST- 2017/07/07 00:00 [received]
PHST- 2018/01/30 00:00 [accepted]
PHST- 2018/03/13 06:00 [pubmed]
PHST- 2019/09/11 06:00 [medline]
PHST- 2018/03/13 06:00 [entrez]
PHST- 2018/07/02 00:00 [pmc-release]
AID - 96139 [pii]
AID - 10.1172/JCI96139 [doi]
PST - ppublish
SO  - J Clin Invest. 2018 Apr 2;128(4):1538-1550. doi: 10.1172/JCI96139. Epub 2018 Mar 
      12.