Version 2 2021-07-01, 22:28Version 2 2021-07-01, 22:28
Version 1 2021-06-16, 21:51Version 1 2021-06-16, 21:51
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posted on 2021-06-25, 00:33authored byMette Q. Ludwig, Petar V. Todorov, Kristoffer L. Egerod, David P. Olson, Tune H. Pers
The dorsal vagal complex
(DVC) in the hindbrain, composed of the area postrema, nucleus of the solitary
tract and dorsal motor nucleus of the vagus, plays a critical role in
modulating satiety. The incretins glucagon-like peptide-1 (GLP-1) and
glucose-dependent insulinotropic polypeptide (GIP) act directly in the brain to
modulate feeding, and receptors for both are expressed in the DVC. Given the
impressive clinical responses to pharmacologic manipulation of incretin
signaling, understanding the central mechanisms by which incretins alter
metabolism and energy balance are of critical importance. Here, we review
recent single-cell approaches used to detect molecular signatures of GLP-1 and
GIP receptor-expressing cells in the DVC. In addition, we discuss how current
advancements in single-cell transcriptomics, epigenetics, spatial
transcriptomics, and circuit mapping techniques have the potential to further
characterize incretin circuits in the hindbrain.
Funding
Novo Nordisk Foundation Center for Basic Metabolic Research is an independent research centre, based at the University of Copenhagen, and partially funded by an unconditional donation from the Novo Nordisk Foundation (https://www.cbmr.ku.dk/; grant no. NNF18CC0034900). We acknowledge the Novo Nordisk Foundation (grant no. NNF16OC0021496 to T.H.P.) and the Lundbeck Foundation (grant no. R190-2014-3904 to T.H.P.). We also acknowledge The Single-Cell Omics Platform at the Novo Nordisk Foundation Center for Basic Metabolic Research for technical expertise and support. Furthermore, this work was supported by a research grant from the Danish Diabetes Academy, which is funded by the Novo Nordisk Foundation (grant no. NNF17SA0031406). Finally, this work has been supported by the National Institute of Diabetes and Digestive and Kidney Diseases (grant no. R01 DK104999 and P01 DK117821).