Inflammation and metabolic disorders

Abstract

Metabolic and immune systems are among the most fundamental requirements for survival. Many metabolic and immune response pathways or nutrient- and pathogen-sensing systems have been evolutionarily conserved throughout species. As a result, immune response and metabolic regulation are highly integrated and the proper function of each is dependent on the other. This interface can be viewed as a central homeostatic mechanism, dysfunction of which can lead to a cluster of chronic metabolic disorders, particularly obesity, type 2 diabetes and cardiovascular disease. Collectively, these diseases constitute the greatest current threat to global human health and welfare.

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Figure 1: Clustering of metabolic diseases.
Figure 2: Evolution of adipose tissue, the liver and the haematopoietic system into distinct organs in mammals.
Figure 3: Architectural organization and proximity of principal metabolic (adipocyte and hepatocyte) and immune (macrophages, Kupffer cells, lymphocytes and dendritic cells) cells in adipose tissue and liver.
Figure 4: Insulin-receptor signalling interfaces with inflammatory signalling at the level of insulin-receptor substrates through activation of serine kinases.
Figure 5: Molecular pathways integrating stress and inflammatory responses with insulin action.
Figure 6: Therapeutic targets at the interface between metabolic and inflammatory pathways.

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Acknowledgements

I am grateful for the contributions of many students and fellows for studies performed in my laboratory. My work is supported by the National Institutes of Health, American Diabetes Foundation, Pew Foundation, Sandler Foundation, Iacocca Foundation and Harvard School of Public Health. I particularly thank K. Freidinger Wellen, M. Gustafson Gregor, U. Ozcan, G. Tuncman, M. Furuhashi and R. Foote for their contributions to this review. Special thanks to D. Hotamisligil for help with illustrations. I apologize to my colleagues whose work I was unable to cite because of space limitations.

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Gökhan Hotamisligil is on the Scientific Advisory Board of Lipomics and is a shareholder of Syndexa Pharmaceuticals.

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Hotamisligil, G. Inflammation and metabolic disorders. Nature 444, 860–867 (2006). https://doi.org/10.1038/nature05485

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