Insulin resistance causes inflammation in adipose tissue

被引：363

作者：

Shimobayashi, Mitsugu ^{[1
]}

Albert, Verena ^{[1
]}

Woelnerhanssen, Bettina ^{[2
]}

Frei, Irina C. ^{[1
]}

Weissenberger, Diana ^{[1
]}

Meyer-Gerspach, Anne Christin ^{[2
]}

Clement, Nicolas ^{[3
]}

Moes, Suzette ^{[1
]}

Colombi, Marco ^{[1
]}

Meier, Jerome A. ^{[1
]}

Swierczynska, Marta M. ^{[1
]}

Jeno, Paul ^{[1
]}

Beglinger, Christoph ^{[2
]}

Peterli, Ralph ^{[3
]}

Hall, Michael N. ^{[1
]}

机构：

[1] Univ Basel, Biozentrum, Basel, Switzerland

[2] St Clara Hosp, Dept Res, Basel, Switzerland

[3] St Clara Hosp, Dept Surg, Basel, Switzerland

来源：

JOURNAL OF CLINICAL INVESTIGATION | 2018年 / 128卷 / 04期

基金：

瑞士国家科学基金会;

关键词：

MONOCYTE CHEMOATTRACTANT PROTEIN-1; TUMOR-NECROSIS-FACTOR; MACROPHAGE ACCUMULATION; WEIGHT-LOSS; OBESITY; GLUCOSE; RICTOR; MTOR; AKT; SENSITIVITY;

D O I：

10.1172/JCI96139

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

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.

引用

页码：1538 / 1550

页数：13

共 71 条

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