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The role of caloric load and mitochondrial homeostasis in the regulation of the NLRP3 inflammasome

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Abstract

Sterile inflammation is a cornerstone of immune activation in obesity and type 2 Diabetes Mellitus. The molecular underpinnings of this inflammation include nutrient excess-mediated activation of the innate immune NLRP3 inflammasome. At the same time, disruption of mitochondrial integrity is emerging as an integral control node in NLRP3 inflammasome activation and is also associated with caloric overload conditions including obesity and diabetes. Conversely, caloric restriction and fasting mimetic interventions alleviate these caloric excess-linked diseases and reduce inflammation and the NLRP3 inflammasome. The objective of this review is to integrate the findings linking mitochondrial integrity to the activation of the NLRP3 inflammasome and to evaluate how caloric restriction or caloric restriction mimetic compounds may play a role in attenuating the NLRP3 inflammasome and sterile inflammation.

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Acknowledgements

This work is funded by the Division of Intramural Research of the National Heart Lung and Blood Institute of the NIH.

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  1. Cardiovascular and Pulmonary Branch, National Heart Lung and Blood Institute, NIH, 10-CRC, Room 5-3150, 10 Center Drive, Bethesda, MD, 20892-1454, USA

    Javier Traba & Michael N. Sack

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Traba, J., Sack, M.N. The role of caloric load and mitochondrial homeostasis in the regulation of the NLRP3 inflammasome. Cell. Mol. Life Sci. 74, 1777–1791 (2017). https://doi.org/10.1007/s00018-016-2431-7

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