Physiology articles within Nature Communications

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  • Article
    | Open Access

    The transcription factor Gcn4 is known to regulate yeast amino acid synthesis. Here, the authors show that Gcn4 also acts as a repressor of protein biosynthesis in a range of conditions that enhance yeast lifespan, such as ribosomal protein knockout, calorie restriction or mTOR inhibition.

    • Nitish Mittal
    • , Joao C. Guimaraes
    •  & Mihaela Zavolan

  • Article
    | Open Access

    Mitochondrial fission and fusion are important mechanisms to maintain mitochondrial function. Here, the authors report that middle-aged flies have more elongated, or ‘hyper-fused’ mitochondria, and show that induction of mitochondrial fission in midlife, but not in early life, extends the health and life of flies.

    • Anil Rana
    • , Matheus P. Oliveira
    •  & David W. Walker

  • Article
    | Open Access

    Advanced maternal age has been associated with lower reproductive success and higher risk of pregnancy complications. Here the authors show that maternal ageing-related embryonic abnormalities in mouse are caused by decidualisation and placentation defects that can be rescued by transferring the embryo from an old to a young uterus.

    • Laura Woods
    • , Vicente Perez-Garcia
    •  & Myriam Hemberger

  • Article
    | Open Access

    The accumulation of senescent cells is thought to contribute to the age-associated decline in tissue function. Here, the authors identify HSP90 inhibitors as a new class of senolytic compounds in an in vitro screening and show that administration of a HSP90 inhibitor reduces age-related symptoms in progeroid mice.

    • Heike Fuhrmann-Stroissnigg
    • , Yuan Yuan Ling
    •  & Paul D. Robbins

  • Article
    | Open Access

    Animal lifespan is plastic and is regulated by conserved signalling pathways. Here, Tikuet al.show that longevity-enhancing mutations or interventions are associated with reduced nucleolar size in worms, flies, mice and humans, and that nucleolar size can predict life-expectancy in individual worms.

    • Varnesh Tiku
    • , Chirag Jain
    •  & Adam Antebi

  • Article
    | Open Access

    The mechanisms that regulate the body’s response to exercise are poorly understood. Here, Rode et al. show that the mechanically activated cation channel Piezo1 is a molecular sensor of physical exercise in the endothelium that triggers endothelial communication to mesenteric vessel muscle cells, leading to vasoconstriction.

    • Baptiste Rode
    • , Jian Shi
    •  & David J. Beech

  • Article
    | Open Access

    Alternative splicing coupled to nonsense-mediated decay (AS-NMD) is a conserved mechanism for post-transcriptional gene regulation. Here, the authors provide evidence that AS-NMD is enhanced during dietary restriction (DR) and is required for DR-mediated longevity assurance in C. elegans.

    • Syed Shamsh Tabrez
    • , Ravi Datta Sharma
    •  & Arnab Mukhopadhyay

  • Article
    | Open Access

    Surface EEG recordings are thought to primarily detect synaptic activity. Here the authors devise an optogenetic method to evoke dendritic calcium spikes in layer 5 pyramidal cells of the rat somatosensory cortex, and report that optogenetically evoked, as well as sensory-evoked dendritic calcium spikes make a significant contribution to surface EEG recordings.

    • Mototaka Suzuki
    •  & Matthew E. Larkum

  • Article
    | Open Access

    Obesity is an established risk factor for pancreatic ductal adenocarcinoma (PDA). Here the authors show that obesity induces the expression of the mitochondrial form of arginase ARG2 in PDA and that ARG2 silencing or loss results in ammonia accumulation and suppression of obesity-driven PDA tumor growth.

    • Tamara Zaytouni
    • , Pei-Yun Tsai
    •  & Nada Y. Kalaany

  • Article
    | Open Access

    The hyperproliferation of vascular smooth muscle cells underlies many vascular diseases. Here Xieet al. show that the splicing factor SRSF1 is an endogenous stimulator of human and mouse aortic smooth muscle cell proliferation via the Δ133p53/EGR1/KLF5 signalling axis, identifying potential therapeutic targets for vascular proliferative disorders.

    • Ning Xie
    • , Min Chen
    •  & Chun-Mei Cao

  • Article
    | Open Access

    Adult mammalian cardiomyocytes are predominantly binucleated and unable to divide. Using single nuclear RNA-sequencing of cardiomyocytes from mouse and human failing and non-failing adult hearts, See et al. show that some cardiomyocytes respond to stress by dedifferentiation and cell cycle re-entry regulated by lncRNAs.

    • Kelvin See
    • , Wilson L. W. Tan
    •  & Roger S. Foo

  • Article
    | Open Access

    Abnormal angiogenesis causes many ocular diseases. Here the authors employ CRISPR/Cas9 gene editing technology to silence VEGFR2, a major regulator of angiogenesis, in retinal endothelium and abrogate angiogenesis in the mouse models of oxygen-induced retinopathy and laser-induced choroid neovascularization.

    • Xionggao Huang
    • , Guohong Zhou
    •  & Hetian Lei

  • Article
    | Open Access

    The angiopoietins regulate vascular maturation, angiogenesis and lymphangiogenesis via their Tie receptors that were long believed to be endothelium-specific. Here the authors show that angiopoietins activate and control pericyte function through pericyte-expressed Tie2 triggering of Calpain, Akt and FOXO3A signalling cascades.

    • Martin Teichert
    • , Laura Milde
    •  & Hellmut G. Augustin

  • Article
    | Open Access

    Numerous genetic variants, including those located in the non-coding regions of the genome, are known to be associated with blood cells traits. Here, Frontini and colleagues investigate their potential regulatory functions using epigenomic data and promoter long-range interactions.

    • Romina Petersen
    • , John J. Lambourne
    •  & Mattia Frontini

  • Article
    | Open Access

    The transcriptional co-activator Prdm16 regulates browning of white adipose tissue (WAT). Here, the authors show that Prdm16 interacts with the transcription factor Hlx, which is stabilized in response to β3-adrenergic signaling, to increase thermogenic gene expression and mitochondrial biogenesis in subcutaneous WAT.

    • Lei Huang
    • , Dongning Pan
    •  & Yong-Xu Wang

  • Article
    | Open Access

    The mechanism by which caffeine, an antagonist of adenosine receptors, regulates metabolism is not clear. Here the authors show that adenosine A1R receptor expression is increased in the hypothalamus of diet-induced obesity mice, and that body weight can be alleviated by central administration of caffeine via its action on hypothalamic oxytocin neurons.

    • Liufeng Wu
    • , Jia Meng
    •  & Guo Zhang

  • Article
    | Open Access

    Glycogen is a storage form of glucose in cells. Here, Gusarovet al. show that glycogen-derived glucose can be used to quickly regenerate the antioxidant glutathione and that inhibiting glycogen synthesis extends C. eleganslifespan, whereas glycogen accumulation drives organismal ageing in worms.

    • Ivan Gusarov
    • , Bibhusita Pani
    •  & Evgeny Nudler

  • Article
    | Open Access

    Non-alcoholic fatty liver disease is more common among older individuals. Here, the authors show that senescent cells in the liver promote fat accumulation and steatosis in the liver, and that clearance of senescent cells reduces hepatic steatosis in old, obese or diabetic mice.

    • Mikolaj Ogrodnik
    • , Satomi Miwa
    •  & Diana Jurk

  • Article
    | Open Access

    Type-2 innate lymphoid cells (ILC2) affect adipose tissue metabolism and function. Here the authors show that the ILC2 are present in para-aortic adipose tissue and represent a major source of IL-5 and IL-13 required for mounting atheroprotective immunity, which can be altered by high fat diet.

    • Stephen A. Newland
    • , Sarajo Mohanta
    •  & Ziad Mallat

  • Article
    | Open Access

    Dysfunction of autophagy in plaque macrophages aggravates atherosclerosis. Here the authors show that induction of macrophage autophagy–lysosomal biogenesis either genetically by overexpression of the master transcriptional regulator of this process, TFEB, or pharmacologically with trehalose is atheroprotective.

    • Ismail Sergin
    • , Trent D. Evans
    •  & Babak Razani

  • Article
    | Open Access

    Type 2 diabetes (T2D) is a heterogeneous disorder characterized by insulin resistance and impaired insulin secretion. Here Axelssonet al. show that Sox5, which is reduced in diabetes, regulates a set of differentially expressed genes in T2D and its genetic and pharmacological induction improves insulin secretion by diabetic islets.

    • A. S. Axelsson
    • , T. Mahdi
    •  & A. H. Rosengren

  • Article
    | Open Access

    Energy consumption in the brain is thought to respond to changes in neuronal activity, without informational role. Here the authors show that increased energy flux in the mushroom body, driven by a pair of input dopaminergic neurons, is a command for the formation of long-term memory in Drosophila.

    • Pierre-Yves Plaçais
    • , Éloïse de Tredern
    •  & Thomas Preat

  • Article
    | Open Access

    The binding of the leukocyte integrin Mac1 to the platelet receptor GPIbα is important for the physiological response to tissue injury. Here the authors show that this interaction also regulates thrombosis, without influencing bleeding time, which may provide clues for the development of new anti-thrombotic drugs.

    • Yunmei Wang
    • , Huiyun Gao
    •  & Daniel I. Simon

  • Article
    | Open Access

    Physical exercise promotes brain angiogenesis through an unknown signalling cascade. Morlandet al. identify the elusive muscle-brain communication and show that lactate produced by muscle activity binds to its receptor HCAR1 in brain vessel-surrounding cells, stimulating VEGF production and brain angiogenesis.

    • Cecilie Morland
    • , Krister A. Andersson
    •  & Linda H. Bergersen

  • Article
    | Open Access

    Lipid turnover in tissues can be calculated from ratios of different carbon isotopes. Here the authors use this approach to study lipid turnover in two distinct adipose tissue depots and find that, in obese individuals, visceral fat is more lipolytic than subcutaneous fat.

    • Kirsty L. Spalding
    • , Samuel Bernard
    •  & Peter Arner

  • Article
    | Open Access

    Demonstrating a causal relationship between cardiac vagal tone and exercise capacity has been previously limited by methodological constraints. Using genetic targeting, silencing and optogenetic recruitment of vagal motor neuron activity in rodents, Machhadaet al. provide direct evidence that vagal drive determines the ability to exercise.

    • Asif Machhada
    • , Stefan Trapp
    •  & Alexander V. Gourine

  • Article
    | Open Access

    Neutrophil adhesion is tightly regulated to enforce protective immunity, but it is unclear how mechanochemical processes such as catch bonds and slip bonds modulate neutrophilsin vivo. Here the authors show that a point mutation in the adhesion molecule L-selectin alters mechanochemical regulation to affect neutrophil functions in mice.

    • Zhenghui Liu
    • , Tadayuki Yago
    •  & Rodger P. McEver

  • Article
    | Open Access

    Germline mutation rates are known to vary between species but somatic mutation rates are less well understood. Here the authors compare mice and humans, observing that somatic mutation rates were nearly two orders of magnitude higher in both species, with both mutation rates significantly higher in mice.

    • Brandon Milholland
    • , Xiao Dong
    •  & Jan Vijg

  • Review Article
    | Open Access

    The brain controls peripheral glucose metabolism, for example by modulating hepatic gluconeogenesis or by regulating glucose uptake into brown adipose tissue. Here, the authors review the brain regions, neurons and molecular mechanisms involved in these processes, and discuss their relevance to disease.

    • Johan Ruud
    • , Sophie M. Steculorum
    •  & Jens C. Brüning

  • Article
    | Open Access

    Interleukin-6 (IL-6) is increased in obesity and activates T cells to promote inflammation. Here, Xuet al. use mice that lack IL-6 receptors on T cells to uncover the temporal and tissue-specific effects of classic and trans IL-6 signalling on inflammation and insulin resistance on a high-fat diet.

    • Elaine Xu
    • , Mafalda M. A. Pereira
    •  & Jens C. Brüning

  • Article
    | Open Access

    The factors that limit the nutrient flexibility of cells remain largely unknown. Here, the authors identify the glutamate/cysteine antiporter xCT in a genetic screen for glucose dependency and show it determines the ability of cells to survive under conditions of low glucose by limiting the utilization of glutamine.

    • Chun-Shik Shin
    • , Prashant Mishra
    •  & David C. Chan

  • Article
    | Open Access

    cAMP/PKA signalling plays important roles in physiology, but there are a lack of tools to spatially distinguish cAMP. Here the authors present a FRET-based cAMP biosensor they call CUTie that can directly compare cAMP signals at multiple subcellular sites and detect nanoscale heterogeneity in cAMP in cardiac myocytes.

    • Nicoletta C. Surdo
    • , Marco Berrera
    •  & Manuela Zaccolo

  • Article
    | Open Access

    Hypothalamus is important for regulating feeding behaviour. Here the authors report genetic identification of neurons in the pretecto-hypothalamic circuit, and their causal involvement in prey detection and prey capture, using a combination of functional imaging and ablation studies in freely swimming zebrafish larvae.

    • Akira Muto
    • , Pradeep Lal
    •  & Koichi Kawakami

  • Article
    | Open Access

    Activation of brown adipose tissue (BAT) reduces the development of atherosclerosis in animal models. Here the authors show that BAT activation also increases reverse cholesterol transport and turnover of high-density lipoprotein, which likely contributes to the anti-atherosclerotic effect of BAT activation.

    • Alexander Bartelt
    • , Clara John
    •  & Joerg Heeren

  • Article
    | Open Access

    LDL receptor-related protein 1 (LRP1) is an endocytic receptor involved in cell signalling and energy homeostasis. Here Maoet al. demonstrate that endothelial Lrp1 modulates lipid and glucose metabolism by binding the nuclear receptor Pparγ and promoting its transcriptional activity.

    • Hua Mao
    • , Pamela Lockyer
    •  & Xinchun Pi

  • Article
    | Open Access

    TNF is typically viewed as an inflammatory mediator. Here the authors identify a non-inflammatory mechanism conserved across species whereby the constitutively expressed smooth muscle cell TNF mediates myogenic signal transduction in skeletal muscle resistance arteries and regulates mean arterial blood pressure.

    • Jeffrey T. Kroetsch
    • , Andrew S. Levy
    •  & Steffen-Sebastian Bolz

  • Article
    | Open Access

    ARPC1B is a component of the actin-related protein 2/3 complex (Arp2/3), which is required for actin filament branching. Kahret al. show that ARPC1B deficiency in humans is associated with severe multisystem disease that includes platelet abnormalities, eosinophilia, eczema and other indicators of immune disease.

    • Walter H. A. Kahr
    • , Fred G. Pluthero
    •  & Aleixo M Muise

  • Article
    | Open Access

    Steviol glycosides are sweet-tasting compounds isolated from a South American shrub and are increasingly used as sweeteners in foods and beverages. Philippaertet al. demonstrate that steviol glycosides potentiate Ca2+-dependent TRPM5 activity and promote glucose-induced insulin secretion and glucose tolerance.

    • Koenraad Philippaert
    • , Andy Pironet
    •  & Rudi Vennekens

  • Article
    | Open Access

    Epithelial progenitor cell growth in the second heart field contributes to heart morphogenesis but how this is regulated at the tissue level is unclear. Here, the authors show that cell elongation, polarized actomyosin and nuclear YAP/TAZ drive epithelial growth and correlate with mechanical tension.

    • Alexandre Francou
    • , Christopher De Bono
    •  & Robert G. Kelly

  • Article
    | Open Access

    The female reproductive tract constitutes the ovary, fallopian tubes, uterus, and cervix, but it is challenging to engineer this systemin vitro. Here, the authors develop a microfluidic device (EVATAR) with reproductive tract and peripheral tissues to replicate hormone release of a 28-day menstrual cycle.

    • Shuo Xiao
    • , Jonathan R. Coppeta
    •  & Teresa K. Woodruff

  • Article
    | Open Access

    De novo lipogenesis is tightly controlled by hormonal and nutritional signals and plays an important role in energy homoeostasis. Here, Liu et al. show that zinc finger protein ZBTB20 regulates the expression of key glycolytic and lipogenic genes by modulating ChREBP expression and transcriptional activity.

    • Gan Liu
    • , Luting Zhou
    •  & Weiping J. Zhang

  • Article
    | Open Access

    The enzyme Atgl participates in the breakdown of lipids in adipose tissue. Here the authors show that pharmacological inhibition of Atgl reduces weight gain and improves metabolic health in mice fed a high-fat diet, without causing adverse effects in cardiac muscle associated with genetic depletion ofAtgl.

    • Martina Schweiger
    • , Matthias Romauch
    •  & Rudolf Zechner

  • Article
    | Open Access

    Emerging evidence suggests that chemical and electrical synapses interact to regulate the strength of synaptic transmission. Liuet al. report that in a C. elegansescape circuit, functionally mixed electrical-chemical synapses exist between premotor interneurons and downstream motor neurons, and that the electrical synapse amplifies the chemical transmission between the neurons.

    • Ping Liu
    • , Bojun Chen
    •  & Zhao-Wen Wang

  • Article
    | Open Access

    It is unclear which progenitors define different regions of the heart. Here, the authors find Secreted frizzled-related protein 5 is expressed in murine progenitor cells for the outflow tract, first heart field, and sinus venosus, but not the right ventricle, and Wnt inhibition prevents progenitor proliferation.

    • Masayuki Fujii
    • , Akane Sakaguchi
    •  & Hiroki Kokubo

  • Article
    | Open Access

    The decline of DNA and protein quality control contributes to organismal ageing. Here, Sonet al. report that nonsense-mediated mRNA decay, a RNA quality control mechanism, is enhanced in long-lived daf-2 mutant worms and contributes to their longevity by regulating expression of the yars-2/tyrosyl tRNA synthetase.

    • Heehwa G. Son
    • , Mihwa Seo
    •  & Seung-Jae V. Lee

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