GPCR-Mediated Signaling of Metabolites

Publication date: 4 April 2017
Source:Cell Metabolism, Volume 25, Issue 4
Author(s): Anna Sofie Husted, Mette Trauelsen, Olga Rudenko, Siv A. Hjorth, Thue W. Schwartz
In addition to their bioenergetic intracellular function, several classical metabolites act as extracellular signaling molecules activating cell-surface G-protein-coupled receptors (GPCRs), similar to hormones and neurotransmitters. "Signaling metabolites" generated from nutrients or by gut microbiota target primarily enteroendocrine, neuronal, and immune cells in the lamina propria of the gut mucosa and the liver and, through these tissues, the rest of the body. In contrast, metabolites from the intermediary metabolism act mainly as metabolic stress-induced autocrine and paracrine signals in adipose tissue, the liver, and the endocrine pancreas. Importantly, distinct metabolite GPCRs act as efficient pro- and anti-inflammatory regulators of key immune cells, and signaling metabolites may thus function as important drivers of the low-grade inflammation associated with insulin resistance and obesity. The concept of key metabolites as ligands for specific GPCRs has broadened our understanding of metabolic signaling significantly and provides a number of novel potential drug targets.

Graphical abstract

Teaser

Husted et al. describe how metabolites act not only as energy sources and building blocks, but as extracellular signaling molecules activating cell-surface GPCRs to control metabolism. "Signaling metabolites" are derived from nutrients, generated by gut microbiota, or function locally as metabolic stress signals and drivers of low-grade inflammation.


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