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Insulin resistance causes inflammation in adipose tissue

Shimobayashi, Mitsugu and Albert, Verena and Woelnerhanssen, Bettina and Frei, Irina C. and Weissenberger, Diana and Meyer-Gerspach, Anne Christin and Clement, Nicolas and Moes, Suzette and Colombi, Marco and Meier, Jerome A. and Swierczynska, Marta M. and Jenö, Paul and Beglinger, Christoph and Peterli, Ralph and Hall, Michael N.. (2018) Insulin resistance causes inflammation in adipose tissue. Journal of Clinical Investigation. pp. 1-32.

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Abstract

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.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Growth & Development > Biochemistry (Hall)
UniBasel Contributors:Hall, Michael N.
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:American Society for Clinical Investigation
ISSN:0021-9738
e-ISSN:1558-8238
Note:Publication type according to Uni Basel Research Database: Journal article
Language:English
Identification Number:
Last Modified:23 Mar 2018 15:19
Deposited On:23 Mar 2018 15:19

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