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      Central and peripheral GLP-1 systems independently suppress eating

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          Abstract

          The anorexigenic peptide glucagon-like peptide-1 (GLP-1) is secreted from gut enteroendocrine cells and brain preproglucagon (PPG) neurons, which respectively define the peripheral and central GLP-1 systems. PPG neurons in the nucleus tractus solitarii (NTS) are widely assumed to link the peripheral and central GLP-1 systems in a unified gut-brain satiation circuit. However, direct evidence for this hypothesis is lacking, and the necessary circuitry remains to be demonstrated. Here we show that PPG NTS neurons encode satiation in mice, consistent with vagal signalling of gastrointestinal distension. However, PPG NTS neurons predominantly receive vagal input from oxytocin receptor-expressing vagal neurons, rather than those expressing GLP-1 receptors. PPG NTS neurons are not necessary for eating suppression by GLP-1 receptor agonists, and concurrent PPG NTS neuron activation suppresses eating more potently than semaglutide alone. We conclude that central and peripheral GLP-1 systems suppress eating via independent gut-brain circuits, providing a rationale for pharmacological activation of PPG NTS neurons in combination with GLP-1 receptor agonists as an obesity treatment strategy.

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          Fiji: an open-source platform for biological-image analysis.

          Fiji is a distribution of the popular open-source software ImageJ focused on biological-image analysis. Fiji uses modern software engineering practices to combine powerful software libraries with a broad range of scripting languages to enable rapid prototyping of image-processing algorithms. Fiji facilitates the transformation of new algorithms into ImageJ plugins that can be shared with end users through an integrated update system. We propose Fiji as a platform for productive collaboration between computer science and biology research communities.
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            Is Open Access

            U1 snRNP regulates cancer cell migration and invasion in vitro

            Stimulated cells and cancer cells have widespread shortening of mRNA 3’-untranslated regions (3’UTRs) and switches to shorter mRNA isoforms due to usage of more proximal polyadenylation signals (PASs) in introns and last exons. U1 snRNP (U1), vertebrates’ most abundant non-coding (spliceosomal) small nuclear RNA, silences proximal PASs and its inhibition with antisense morpholino oligonucleotides (U1 AMO) triggers widespread premature transcription termination and mRNA shortening. Here we show that low U1 AMO doses increase cancer cells’ migration and invasion in vitro by up to 500%, whereas U1 over-expression has the opposite effect. In addition to 3’UTR length, numerous transcriptome changes that could contribute to this phenotype are observed, including alternative splicing, and mRNA expression levels of proto-oncogenes and tumor suppressors. These findings reveal an unexpected role for U1 homeostasis (available U1 relative to transcription) in oncogenic and activated cell states, and suggest U1 as a potential target for their modulation.
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              BORIS: a free, versatile open-source event-logging software for video/audio coding and live observations

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                Author and article information

                Journal
                101736592
                Nat Metab
                Nat Metab
                Nature metabolism
                2522-5812
                26 January 2021
                01 February 2021
                15 February 2021
                15 August 2021
                : 3
                : 2
                : 258-273
                Affiliations
                [1 ]Centre for Cardiovascular and Metabolic Neuroscience, Department of Neuroscience, Physiology and Pharmacology, University College London, UK
                [2 ]Department of Psychology, Program in Neuroscience, Florida State University, USA
                [3 ]Department of Pharmacodynamics, University of Florida, USA
                [4 ]Department of Health Sciences and Technology, ETH Zurich, Switzerland
                [5 ]Department of Physiology and Functional Genomics, University of Florida, USA
                [6 ]Institute of Metabolic Science, University of Cambridge, UK
                [7 ]Center for Integrative Cardiovascular and Metabolic Disease, University of Florida, USA
                Author notes
                Article
                EMS114742
                10.1038/s42255-021-00344-4
                7116821
                33589843
                bb83c1b0-70d1-4f1b-be5a-5f139c78bd3a

                Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms

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                Categories
                Article

                glucagon-like peptide-1,preproglucagon,oxytocin,nucleus tractus solitarius, vagal afferent neurons,eating,feeding,satiation,behavioural satiety sequence,semaglutide

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