Metabolic Receptology in the Schwartz Group

The aim of the Schwartz Group is to characterize and understand how signaling metabolites and their specific GPCR sensors interact with hormonal and neuronal mechanism to control endocrine and metabolic functions as the basis for developing novel means to prevent and treat obesity and diabetes. 

Research focus

Metabolites are not just fuel and metabolic building blocks. It is becoming increasingly clear that key metabolites generated from dietary nutrients, from gut microbiota and from our intermediary metabolism also function as extracellular mediators that are recognized by and signal through specific GPCRs in a manner very similar to hormones and neurotransmitters. The metabolite GPCRs are highly expressed on metabolic and endocrine cells as well as leukocytes. The overarching hypothesis of the Schwartz Group is that ‘signaling metabolites’ function as important stress and fuel signals which in an autocrine manner through their GPCRs regulate the function of the metabolic and endocrine cells themselves and in a paracrine manner regulate the function of neighboring cells including immune cells.

A major strength of the group is to work not only with genetic models but also in close collaboration with the Frimurer group to develop novel non-metabolite ligands for metabolite GPCRs which can mimic or block the effect of the signaling metabolites and be used as pharmacological tools and as leads in drug discovery.

Main findings

“GPCR-Mediated Signaling of Metabolites”
Published in Cell Metabolism in 2017 this review gives a comprehensive overview of a signaling metabolites and their roles as extracellular signaling agents controlling metabolic, endocrine, and immune cell function through their cognate cell surface GPCRs,

“Receptor structure-based discovery of non-metabolite agonists for the succinate receptor GPR91”
In this article published in Molecular Metabolism in 2017 we describe the discovery of novel, synthetic non-metabolite agonists for GPR91which will be valuable as pharmacological tools and as leads for the development of drugs to treat low grade metabolic inflammation and diabetic complications such as retinopathy and nephropathy.

“Enterochromaffin 5-HT Cells – a Major Target for GLP-1 and Gut Microbial Metabolites”
In this article published in Molecular Metabolism in 2018 it is discovered how the most abundant enteroendocrine cell type senses nutrient metabolites indirectly through GLP-1 cells and the differential expression of GPCRs in 5-HT cells of the colon versus the small intestine is used to identify novel receptors through which gut microbial metabolites affect host metabolism.

Staff of the Schwartz Group

Group leader: Professor Thue W. Schwartz