Physiological role of cytokines in the regulation of mammalian metabolism

Abstract

The innate cytokine system is involved in the response to excessive food intake. In this review, we highlight recent advances in our understanding of the physiological role of three prominent cytokines, interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF), in mammalian metabolic regulation. This recent research highlights the pleiotropic and context-dependent functions in the immune-metabolic interplay. IL-1β is activated in response to overloaded mitochondrial metabolism, stimulates insulin secretion, and allocates energy to immune cells. IL-6 is released by contracting skeletal muscle and adipose tissue and directs energy from storing tissues to consuming tissues. TNF induces insulin resistance and prevents ketogenesis. Additionally, the therapeutic potential of modulating the activity of each cytokine is discussed.

Trial registration: ClinicalTrials.gov NCT00303394 NCT03534297 NCT05435742.

Keywords: cytokine; diabetes; humans; insulin; metabolism; obesity.