Abstract
Diabetes mellitus is one of the most common chronic metabolic disorders worldwide, and its incidence in Asian countries is alarmingly high. Type 2 diabetes (T2DM) is closely associated with obesity, and the staggering rise in obesity is one of the primary factors related to the increased frequency of T2DM. Low-grade chronic inflammation is also accepted as an integral metabolic adaption in obesity and T2DM, and is believed to be a major player in the onset of insulin resistance. However, the exact mechanism(s) that cause a persistent chronic low-grade infiltration of leukocytes into insulin-target tissues such as adipose, skeletal muscle and liver are not entirely known. Recent developments in the understanding of leukocyte metabolism have revealed that the inflammatory polarization of immune cells, and consequently their immunological function, are strongly connected to their metabolic profile. Therefore, it is hypothesized that dysfunctional immune cell metabolism is a central cellular mechanism that prevents the resolution of inflammation in chronic metabolic conditions such as that observed in obesity and T2DM. The purpose of this review is to explore the metabolic demands of different immune cell types, and identify the molecular switches that control immune cell metabolism and ultimately function. Understanding of these concepts may allow the development of interventions that can correct immune function and may possibly decrease chronic low-grade inflammation in humans suffering from obesity and T2DM. We also review the latest clinical techniques used to measure metabolic flux in primary leukocytes isolated from obese and T2DM patients.
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Acknowledgements
We thank the School of Biomedical Sciences and School of Public Health in the Faculty of Health Sciences at Curtin University, along with Telethon Kids Institute, University of Western Australia, Perth, Australia for research support. Curtin Health Innovation Research Institute (CHIRI) is acknowledged with thanks for access to excellent research facilities. EKC is the recipient of an Australian postgraduate scholarship award (APA).
Author contributions
The present work was designed by KNK. Initial manuscript preparation and draft was undertaken by KNK, EKC and PHH, and subsequently revised by RC and PN. Figures were designed by KNK, EKC and RC, and prepared by KNK and EKC. All authors approved the final version of the paper.
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Keane, K., Calton, E., Carlessi, R. et al. The bioenergetics of inflammation: insights into obesity and type 2 diabetes. Eur J Clin Nutr 71, 904–912 (2017). https://doi.org/10.1038/ejcn.2017.45
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DOI: https://doi.org/10.1038/ejcn.2017.45
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