Physiology articles within Nature Communications

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  • Article
    | Open Access

    The α-cardiac actin M305L hypertrophic cardiomyopathy-causing mutation is located near residues that help confine tropomyosin to an inhibitory position along thin filaments. Here the authors assessed M305L actin in vivo, in vitro, and in silico to characterize emergent pathological properties and define the mechanistic basis of disease.

    • Meera C. Viswanathan
    • , William Schmidt
    •  & Anthony Cammarato

  • Article
    | Open Access

    The regulatory networks that govern chromatin accessibility and gene expression in brown and beigeadipocytes remain to be fully elucidated. Here the authors use fat-specific inactivation of BAF60a toreveal a differential role for this chromatin remodeling factor in brown fat thermogenesis and coldinduced browning of inguinal fat.

    • Tongyu Liu
    • , Lin Mi
    •  & Siming Li

  • Article
    | Open Access

    Adipose tissue expansion occurs via enlargement of adipocytes as well as the generation of new fat cells, the latter being associated with more favorable metabolic outcomes. Here, the authors show that activation of adipocyte Piezo1 results in release of FGF1 and stimulates the differentiation of adipocyte precursor cells.

    • ShengPeng Wang
    • , Shuang Cao
    •  & Stefan Offermanns

  • Article
    | Open Access

    Runx2 is essential for tuning the generation of bone from skeletal stem cells (SSCs). Here, the authors demonstrate that the CK2/HAUSP pathway stabilizes RUNX2 protein thereby regulating the commitment of SSCs to osteoprogenitors as well as their subsequent maturation, and that inhibition of this pathway can block heterotopic ossification.

    • Jung-Min Kim
    • , Yeon-Suk Yang
    •  & Jae-Hyuck Shim

  • Article
    | Open Access

    Structural changes to the left ventricle are characteristic of dilated cardiomyopathy (DCM), a disease for which many rare genetic variants are known. Here, Pirruccello et al. report GWAS of seven cardiac MRI measurements in the left ventricle and describe shared loci and polygenic association with DCM.

    • James P. Pirruccello
    • , Alexander Bick
    •  & Krishna G. Aragam

  • Article
    | Open Access

    Dysregulated prefrontal control over amygdala has been implicated in the etiology of stress-related psychiatric disorders. Here, the authors show that the dysregulation preferentially occurs in amygdala neurons that are mono- but not bi-directionally connected with dorsomedial prefrontal cortex.

    • Wei-Zhu Liu
    • , Wen-Hua Zhang
    •  & Bing-Xing Pan

  • Article
    | Open Access

    Arterial degeneration, closely associated with cardiovascular diseases, is driven by aging-related vascular cell-specific transcriptomics changes. This study provides a single-cell transcriptomic atlas for senile aortic and coronary arteries and underscores FOXO3A-based the transcriptional network in vasoprotection during aging.

    • Weiqi Zhang
    • , Shu Zhang
    •  & Jing Qu

  • Article
    | Open Access

    Brown adipose tissue, known produce heat by metabolizing fat, is also secretes molecules capable of communicating with other organs. Here the authors show that brown adipose tissue secretes kininogen, a component of heat system regulation, that provides auto-regulatory inhibitory signaling in brown adipose tissue.

    • Marion Peyrou
    • , Rubén Cereijo
    •  & Francesc Villarroya

  • Article
    | Open Access

    Hepatokines are proteins secreted by the liver that can regulate whole body metabolism. Here the authors identify apolipoprotein J as a hepatokine that regulates muscle glucose metabolism and insulin resistance through a low-density lipoprotein receptor-related protein−2 mediated mechanism in mice.

    • Ji A Seo
    • , Min-Cheol Kang
    •  & Young-Bum Kim

  • Article
    | Open Access

    Disruption of different components of molecular circadian clocks has varying effects on health and lifespan of model organisms. Here the authors show that loss of period extends life in drosophila melanogaster.

    • Matt Ulgherait
    • , Anna Chen
    •  & Mimi Shirasu-Hiza

  • Article
    | Open Access

    Overnutrition is associated with hypothalamic ER stress and impaired leptin signaling. Here the authors show that ER stress already occurs in neonates and that treatment with the ER stress relieving drug TUDCA early in life has beneficial metabolic and neurodevelopmental effects.

    • Soyoung Park
    • , Aleek Aintablian
    •  & Sebastien G. Bouret

  • Article
    | Open Access

    Cardiovascular risks of cold exposure and the subsequent activation of the β3-AR pathway limit the application of beige fat thermogenesis for the treatment of obesity. Here, the authors show that optogenetics light-activated Ca2+ cycling in adipocytes triggers a fat-specific “cold-mimetic” thermogenesis response protecting mice against diet-induced obesity.

    • Kazuki Tajima
    • , Kenji Ikeda
    •  & Shingo Kajimura

  • Article
    | Open Access

    Vitamin D is a precursor of the steroid hormone 1,25-dihydroxyvitamin D3, and its deficiency is associated with many adverse health outcomes. Here, Revez et al. perform a genome-wide association study for circulating 25-hydroxyvitamin D in 417,580 individuals and test for potential causal relationships with other traits using Mendelian randomization.

    • Joana A. Revez
    • , Tian Lin
    •  & John J. McGrath

  • Article
    | Open Access

    Acellular tissue engineered vessels functionalised with VEGF are coated with a layer of endothelial cells after in vivo implantation, but the source of the cells are unknown. Here the authors provide evidence that monocytes expressing VEGF receptors can transdifferentiate into endothelial cells via a macrophage intermediate.

    • Randall J. Smith Jr.
    • , Bita Nasiri
    •  & Stelios T. Andreadis

  • Article
    | Open Access

    The molecular basis of activin receptor-like kinase 1 (ALK1)-mediated endothelial bone morphogenetic protein (BMP) signalling is not fully understood. Here, the authors present crystal structures of the BMP10:ALK1 and prodomain-bound BMP9:ALK1 complexes, providing mechanistic insights into ALK1 signalling specificity.

    • Richard M. Salmon
    • , Jingxu Guo
    •  & Wei Li

  • Article
    | Open Access

    Exercise has been shown to be an effective approach to ameliorate metabolic disease in mice housed at ambient temperatures, a condition of mild cold stress to mice. Here the authors show that molecular and metabolic adaptations to exercise are blunted when mice are housed in thermoneutral conditions.

    • Steffen H. Raun
    • , Carlos Henriquez-Olguín
    •  & Lykke Sylow

  • Article
    | Open Access

    Aging involves gradual loss of tissue function, and transcription factor (TF) expression can ameliorate this in progeroid mice. Here the authors show that transient TF expression reverses age-associated epigenetic marks, inflammatory profiles and restores regenerative potential in naturally aged human cells.

    • Tapash Jay Sarkar
    • , Marco Quarta
    •  & Vittorio Sebastiano

  • Article
    | Open Access

    Age at voice-breaking is used to determine puberty timing in men, recall of which is considered less accurate than age at first menarche in women. Here, the authors perform multi-trait GWAS for male puberty timing by including both age at voice breaking and age of first facial hair for improved phenotype definition and power.

    • Ben Hollis
    • , Felix R. Day
    •  & John R. B. Perry

  • Article
    | Open Access

    Leptin regulates the sympathetic nervous system, energy expenditure and body weight through incompletely understood mechanisms. Here the authors report that Sh2b1 in leptin receptor positive neurons mediates the ability of leptin to stimulate sympathetic nerve activity in brown adipose tissue, body temperature and cold tolerance.

    • Lin Jiang
    • , Haoran Su
    •  & Liangyou Rui

  • Article
    | Open Access

    Genetic variants in the FAM13A locus have been associated with anthropometric and glycemic traits. Here, using fine-mapping, in vitro knockdown studies in pre-adipocytes and in vivo knockout in mice, the authors show that FAM13A is involved in regulating fat distribution and metabolic traits.

    • Mohsen Fathzadeh
    • , Jiehan Li
    •  & Joshua W. Knowles

  • Article
    | Open Access

    Uncoupling protein-1 (UCP1) plays a central role in energy dissipation in brown adipose tissue. Here the authors show that FGF6 and FGF9 induce UCP1 expression in adipocytes and preadipocytes, via modulation of a transcriptional network that is dissociated from brown adipogenesis.

    • Farnaz Shamsi
    • , Ruidan Xue
    •  & Yu-Hua Tseng

  • Article
    | Open Access

    Genome-scale models of microbial metabolism largely ignore reaction kinetics. Here, the authors develop a general mathematical framework for modeling cellular growth with explicit non-linear reaction kinetics and use it to glean insights into the principles of cellular resource allocation and growth.

    • Hugo Dourado
    •  & Martin J. Lercher

  • Article
    | Open Access

    The roots of psychopathology take shape during adverse parent-infant interactions, shown through infant attachment quality. Using rodents, the authors show that blunted infant cortical processing of the mother determines attachment quality through a stress hormone-dependent mechanism.

    • Maya Opendak
    • , Emma Theisen
    •  & Regina M. Sullivan

  • Article
    | Open Access

    Phosphocreatine plays a vital role in cellular energetic homeostasis, but there are no routine diagnostic tests to noninvasively map the distribution with clinically relevant spatial resolution. Here, the authors develop and validate a noninvasive approach for quantifying and imaging phosphocreatine, without contrast agents, on widely available clinical MRI scanners with artificial neural networks.

    • Lin Chen
    • , Michael Schär
    •  & Jiadi Xu

  • Article
    | Open Access

    Metabolic adaptation to different diets results in changes to gene expression. Here, the authors characterise the chromatin landscape and transcriptional network in mice on a diet of high saturated fat, compared to a diet high in carbohydrate, finding a dramatic reprogramming of the liver transcriptional network.

    • Yufeng Qin
    • , Sara A. Grimm
    •  & Paul A. Wade

  • Article
    | Open Access

    In response to insulin, liver cells increase de novo lipogenesis via the transcription factors USF-1 and SREBP. Here the authors show that USF-1 recruits JMJD1C, after its phosphorylation by mTOR, to lipogenic promoters where JMJD1C demethylates histone H3, contributing to lipogenesis by an epigenetic mechanism.

    • Jose A. Viscarra
    • , Yuhui Wang
    •  & Hei Sook Sul

  • Article
    | Open Access

    Ammonia oxidizing archaea and Nitrospinae are the main known nitrifiers in the ocean, but the much greater abundance of the former is puzzling. Here, the authors show that differences in mortality, rather than thermodynamics, cell size or biomass yield, explain the discrepancy, without the need to invoke yet undiscovered, abundant nitrite oxidizers.

    • Katharina Kitzinger
    • , Hannah K. Marchant
    •  & Marcel M. M. Kuypers

  • Article
    | Open Access

    Whether the immune system aging differs between men and women is barely known. Here the authors characterize gene expression, chromatin state and immune subset composition in the blood of healthy humans 22 to 93 years of age, uncovering shared as well as sex-unique alterations, and create a web resource to interactively explore the data.

    • Eladio J. Márquez
    • , Cheng-han Chung
    •  & Duygu Ucar

  • Article
    | Open Access

    Extracellular vesicles (EVs) containing miRNAs or proteins can coordinate metabolic responses between tissues. Here the authors demonstrate that during lipid overload, the liver secretes miRNA-containing EVs through a Ggpps-Rab27 dependent mechanism, which controls adipose tissue lipid storage capacity.

    • Yue Zhao
    • , Meng-Fei Zhao
    •  & Chao-Jun Li

  • Article
    | Open Access

    Production of inflammatory mediators by M1-polarized macrophages is thought to rely on suppression of mitochondrial metabolism in favor of glycolysis. Refining this concept, here the authors define metabolic targets of nitric oxide as responsible for the mitochondrial rewiring resulting from polarization.

    • Erika M. Palmieri
    • , Marieli Gonzalez-Cotto
    •  & Daniel W. McVicar

  • Article
    | Open Access

    Mutations in the hexosamine pathway key enzyme glutamine fructose-6-phosphate amidotransferase (GFAT-1) improve protein quality control and extend C. elegans lifespan. Here the authors present the crystal structures of full-length human GFAT-1 alone and with bound ligands and perform activity assays, which show that gain-of-function in the longevity-associated G451E variant is caused by a loss of feedback regulation.

    • Sabine Ruegenberg
    • , Moritz Horn
    •  & Martin S. Denzel

  • Article
    | Open Access

    Brown adipose thermogenesis increases energy expenditure and relies on uncoupling protein 1 (UCP1), however, UCP1 knock-out mice show resistance to diet-induced obesity at room temperature. Here, the authors show that this resistance relies on FGF21-signaling, inducing the browning of white adipose tissue.

    • Susanne Keipert
    • , Dominik Lutter
    •  & Martin Jastroch

  • Comment
    | Open Access

    Understanding the cellular adaptation to oxygen deficiency -hypoxia- has a profound impact on our knowledge of the pathogenesis of several diseases. The elucidation of the molecular machinery that regulates response to hypoxia has been awarded the Nobel Prize in Physiology or Medicine.

    • José López-Barneo
    •  & M. Celeste Simon

  • Article
    | Open Access

    Serotonin inhibits adipose tissue thermogenesis. Here the authors show that obese mice housed in thermoneutrality have increased mast cell serotonin synthesis, and that inhibiting this pathway through deletion of mast cell Tph1 increases white adipose tissue browning and protects against diet-induced obesity, insulin resistance and liver steatosis.

    • Julian M. Yabut
    • , Eric M. Desjardins
    •  & Gregory R. Steinberg

  • Article
    | Open Access

    AgRP-expressing neurons regulate feeding, glucose homeostasis and locomotor activity, but the neurotransmitters that mediate these effects are unclear. Here the authors show that neuropeptide Y in these neurons regulates rapid feeding responses and insulin sensitivity, but not locomotor activity.

    • Linda Engström Ruud
    • , Mafalda M. A. Pereira
    •  & Jens C. Brüning

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