Regulation of Adipose Tissue Inflammation and Insulin Resistance by MAPK Phosphatase 5.
Obesity and metabolic disorders such as insulin resistance and type 2 diabetes have become a major threat to public health globally. The mechanisms that lead to insulin resistance in type 2 diabetes have not been well understood. In this study, we show that mice deficient in MAPK phosphatase 5 (MKP5) develop insulin resistance spontaneously at an early stage of life and glucose intolerance at a later age. Increased macrophage infiltration in white adipose tissue of young MKP5-deficient mice correlates with the development of insulin resistance. Glucose intolerance in MKP5-deficient mice is accompanied by significantly increased visceral adipose weight, reduced AKT activation, enhanced p38 activity, and increased inflammation in visceral adipose tissue when compared with wild-type (WT) mice. Deficiency of MKP5 resulted in increased inflammatory activation in macrophages. These findings thus demonstrate that MKP5 critically controls inflammation in white adipose tissue and the development of metabolic disorders.
From the Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore, the Immunology Programme, Life Science Institute, National University of Singapore, Singapore 117597, Singapore.
Yongliang
Y
Zhang
the Department of Immunology, University of Washington, Seattle, Washington 98195.
Thang
T
Nguyen
From the Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore, the Immunology Programme, Life Science Institute, National University of Singapore, Singapore 117597, Singapore.
Peng
P
Tang
the Howard Hughes Medical Institute, University of Massachusetts, Worcester, Massachusetts 01606.
Norman J
NJ
Kennedy
From the Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore, the Immunology Programme, Life Science Institute, National University of Singapore, Singapore 117597, Singapore.
Huipeng
H
Jiao
the Department of Endocrinology and Metabolism, Shanghai Jiaotong University Affiliated Sixth People's Hospital, Shanghai Diabetes Institute, Shanghai Clinical Center of Diabetes, Shanghai 200233, China.
Mingliang
M
Zhang
the Department of Immunology, MD Anderson Cancer Center, Houston, Texas 77054.
Joseph M
JM
Reynolds
the Pathobiology and Molecular Medicine Graduate Program, University of Cincinnati, Ohio 45215.
Anja
A
Jaeschke
the Department of Immunology, MD Anderson Cancer Center, Houston, Texas 77054.
Natalia
N
Martin-Orozco
the Department of Immunology, MD Anderson Cancer Center, Houston, Texas 77054.
Yeonseok
Y
Chung
the Center for Environmental and Genetic Medicine, Institute of Biosciences and Technology, Texas A&M University System Health Sciences Center, Houston, Texas 77030.
Wei-min
WM
He
the Department of Endocrinology and Metabolism, Shanghai Jiaotong University Affiliated Sixth People's Hospital, Shanghai Diabetes Institute, Shanghai Clinical Center of Diabetes, Shanghai 200233, China.
Chen
C
Wang
the Department of Endocrinology and Metabolism, Shanghai Jiaotong University Affiliated Sixth People's Hospital, Shanghai Diabetes Institute, Shanghai Clinical Center of Diabetes, Shanghai 200233, China.
Weiping
W
Jia
the Laboratory of Signal Transduction, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Shanghai Jiao-Tong University School of Medicine, Shanghai 200025, China.
Baoxue
B
Ge
the Howard Hughes Medical Institute, University of Massachusetts, Worcester, Massachusetts 01606.
Roger J
RJ
Davis
the Department of Immunology, Howard Hughes Medical Institute, Yale University, New Haven, Connecticut 06520, and Richard.flavell@yale.edu.
Richard A
RA
Flavell
the Institute for Immunology, Tsinghua University, Beijing 100084, China chendong@tsinghua.edu.cn.
Chen
C
Dong
D000273:Adipose Tissue / Q000201:enzymology / Q000473:pathology*; D000818:Animals; D005947:Glucose / Q000378:metabolism; D007249:Inflammation / Q000201:enzymology*; D007333:Insulin Resistance; D008264:Macrophages / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D054639:Mitogen-Activated Protein Kinase Phosphatases / Q000235:genetics / Q000378:metabolism*
D054639:Mitogen-Activated Protein Kinase Phosphatases; D005947:Glucose
MAPK phosphatase; inflammation; insulin resistance; obesity; type 2 diabetes