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      Turn it off and on again: characteristics and control of torpor

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          Abstract

          Torpor is a hypothermic, hypoactive, hypometabolic state entered into by a wide range of animals in response to environmental challenge. This review summarises the current understanding of torpor. We start by describing the characteristics of the wide-ranging physiological adaptations associated with torpor. Next follows a discussion of thermoregulation, control of food intake and energy expenditure, and the interactions of sleep and thermoregulation, with particular emphasis on how those processes pertain to torpor. We move on to take a critical view of the evidence for the systems that control torpor entry, including both the efferent circulating factors that signal the need for torpor, and the central processes that orchestrate it. Finally, we consider how the putative circuits responsible for torpor induction integrate with the established understanding of thermoregulation under non-torpid conditions and highlight important areas of uncertainty for future studies.

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          Most cited references208

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          Molecular, spatial and functional single-cell profiling of the hypothalamic preoptic region

          The hypothalamus controls essential social behaviors and homeostatic functions. However, the cellular architecture of hypothalamic nuclei, including the molecular identity, spatial organization, and function of distinct cell types, is poorly understood. Here, we developed an imaging-based in situ cell type identification and mapping method and combined it with single-cell RNA-sequencing to create a molecularly annotated and spatially resolved cell atlas of the mouse hypothalamic preoptic region. We profiled ~1 million cells, identified ~70 neuronal populations characterized by distinct neuromodulatory signatures and spatial organizations, and defined specific neuronal populations activated during social behaviors in male and female mice, providing a high-resolution framework for mechanistic investigation of behavior circuits. The approach described opens a new avenue for the construction of cell atlases in diverse tissues and organisms.
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            Evolving the lock to fit the key to create a family of G protein-coupled receptors potently activated by an inert ligand.

            We evolved muscarinic receptors in yeast to generate a family of G protein-coupled receptors (GPCRs) that are activated solely by a pharmacologically inert drug-like and bioavailable compound (clozapine-N-oxide). Subsequent screening in human cell lines facilitated the creation of a family of muscarinic acetylcholine GPCRs suitable for in vitro and in situ studies. We subsequently created lines of telomerase-immortalized human pulmonary artery smooth muscle cells stably expressing all five family members and found that each one faithfully recapitulated the signaling phenotype of the parent receptor. We also expressed a G(i)-coupled designer receptor in hippocampal neurons (hM(4)D) and demonstrated its ability to induce membrane hyperpolarization and neuronal silencing. We have thus devised a facile approach for designing families of GPCRs with engineered ligand specificities. Such reverse-engineered GPCRs will prove to be powerful tools for selectively modulating signal-transduction pathways in vitro and in vivo.
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              Anatomy and regulation of the central melanocortin system.

              Roger Cone (2005)
              The central melanocortin system is perhaps the best-characterized neuronal pathway involved in the regulation of energy homeostasis. This collection of circuits is unique in having the capability of sensing signals from a staggering array of hormones, nutrients and afferent neural inputs. It is likely to be involved in integrating long-term adipostatic signals from leptin and insulin, primarily received by the hypothalamus, with acute signals regulating hunger and satiety, primarily received by the brainstem. The system is also unique from a regulatory point of view in that it is composed of fibers expressing both agonists and antagonists of melanocortin receptors. Given that the central melanocortin system is an active target for development of drugs for the treatment of obesity, diabetes and cachexia, it is important to understand the system in its full complexity, including the likelihood that the system also regulates the cardiovascular and reproductive systems.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Data CurationRole: Funding AcquisitionRole: Writing – Original Draft PreparationRole: Writing – Review & Editing
                Role: Writing – Review & Editing
                Role: Writing – Review & Editing
                Journal
                Wellcome Open Res
                Wellcome Open Res
                Wellcome Open Research
                F1000 Research Limited (London, UK )
                2398-502X
                17 November 2021
                2021
                : 6
                : 313
                Affiliations
                [1 ]School of Physiology, Pharmacology, & Neuroscience, University of Bristol, Bristol, Bristol, BS8 1TD, UK
                [1 ]Centre for Biological Timing, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK
                [1 ]Department of Chemistry and Biochemistry, Institute of Arctic Biology, Center for Transformative Research in Metabolism, University of Alaska Fairbanks, Fairbanks, AK, USA
                [1 ]Department of Neurological Surgery, Oregon Health & Science University, Portland, OR, USA
                [1 ]Whitehead Institute for Biomedical Research, Cambridge, MA, USA
                [2 ]Massachusetts Institute of Technology, Cambridge, MA, USA
                [3 ]Harvard Medical School, Boston, MA, USA
                School of Physiology, Pharmacology and Neuroscience, University of Bristol, UK
                Author notes

                No competing interests were disclosed.

                Competing interests: No competing interests were disclosed.

                Competing interests: I have financial interest in Be Cool Pharmaceutics

                Competing interests: No competing interests were disclosed.

                Competing interests: No competing interests were disclosed.

                Competing interests: none

                Author information
                https://orcid.org/0000-0001-7884-6522
                https://orcid.org/0000-0002-9296-3482
                https://orcid.org/0000-0003-0345-0456
                Article
                10.12688/wellcomeopenres.17379.1
                8764563
                35087956
                4d7d3147-f7cb-45c2-8920-f084aa7923fb
                Copyright: © 2021 Ambler M et al.

                This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 12 November 2021
                Funding
                Funded by: Wellcome Trust
                Award ID: 211029
                This work was supported by Wellcome [211029 <a href=https://doi.org/10.35802/211029>https://doi.org/10.35802/211029</a>].
                The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Review
                Articles

                torpor,metabolism,homeostasis,thermoregulation,hibernation,energy balance

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