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Immunologic impact of the intestine in metabolic disease
Daniel A. Winer, … , Helen J. Dranse, Tony K.T. Lam
Daniel A. Winer, … , Helen J. Dranse, Tony K.T. Lam
Published January 3, 2017
Citation Information: J Clin Invest. 2017;127(1):33-42. https://doi.org/10.1172/JCI88879.
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Review Series

Immunologic impact of the intestine in metabolic disease

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Abstract

Obesity and diabetes are associated with increased chronic low-grade inflammation and elevated plasma glucose levels. Although inflammation in the fat and liver are established features of obesity-associated insulin resistance, the intestine is emerging as a new site for immunologic changes that affect whole-body metabolism. Specifically, microbial and dietary factors incurred by diet-induced obesity influence underlying innate and adaptive responses of the intestinal immune system. These responses affect the maintenance of the intestinal barrier, systemic inflammation, and glucose metabolism. In this Review we propose that an understanding of the changes to the intestinal immune system, and how these changes influence systemic immunity and glucose metabolism in a whole-body integrative and a neuronal-dependent network, will unveil novel intestinal pathologic and therapeutic targets for diabetes and obesity.

Authors

Daniel A. Winer, Shawn Winer, Helen J. Dranse, Tony K.T. Lam

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Figure 2

An integrative and neuronal-dependent intestinal immunologic and metabolic network.

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An integrative and neuronal-dependent intestinal immunologic and metabol...
We propose that the intestine senses a change in the level of nutrients, cytokines, and microbiota-derived SCFAs, which triggers a gut/brain CCK- and GLP-1–dependent axis to regulate systemic inflammatory and glucose homeostasis. We further postulate that this proposed integrative and neuronal-dependent network is altered in obesity and diabetes and is targeted by metformin and bariatric surgical therapies to restore systemic metabolic homeostasis. In parallel, an influx of intestinal nutrients, bacterial products, and cytokines into the blood circulation induces inflammation and insulin resistance in the VAT and the liver and disrupts glucose homeostasis in obesity and diabetes.

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ISSN: 0021-9738 (print), 1558-8238 (online)

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