Physiology articles within Nature Communications

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  • 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

  • Article
    | Open Access

    Healthspan and healthy aging are areas of research with potential socioeconomic impact. Here, the authors present the Medical Genome Reference Bank (MGRB) which consist of over 4,000 individuals aged 70 years and older without a history of the major age-related diseases and report on results from whole-genome sequencing and association analyses.

    • Mark Pinese
    • , Paul Lacaze
    •  & David M. Thomas

  • Article
    | Open Access

    Beliefs that justify the economic system buffer against the aversive emotional impact of inequality. Here the authors show that system-justifying economic ideology predicts dampened negativity, measured using self-reported and physiological responses, to manifestations of poverty and wealth.

    • Shahrzad Goudarzi
    • , Ruthie Pliskin
    •  & Eric D. Knowles

  • Article
    | Open Access

    As an interface between maternal and fetal tissues, decidua hosts immune cells specialized in fostering a successful pregnancy. Here the authors carry out high-dimensional characterization of function, morphology and surface markers of human decidual innate lymphoid cells (ILCs), identifying subsets with features distinct from blood ILC.

    • Oisín Huhn
    • , Martin A. Ivarsson
    •  & Francesco Colucci

  • Article
    | Open Access

    Mendelian randomization (MR) is a method for inferring causal relationships between risk factors and outcomes via associated genetic variants. Here, Burgess et al. develop the contamination mixture method which yields robust MR results in the presence of invalid instrumental variables and groups variants by their effect estimates.

    • Stephen Burgess
    • , Christopher N Foley
    •  & Joanna M. M. Howson

  • Article
    | Open Access

    A difference in the survival of respiratory chain complex III deficient Bcs1lp.S78G mice was observed between two congenic mouse strains. Here the authors show how in one of the strains the combined effects of a spontaneously arising non-pathogenic variant and the disease-causing Bcs1lp.S78G mutation exacerbate CIII deficiency and disease progression.

    • Janne Purhonen
    • , Vladislav Grigorjev
    •  & Jukka Kallijärvi

  • Article
    | Open Access

    Mechanical forces induce bone remodeling, but how bone cells sense mechanical signaling is unclear. Here, the authors show that loss of the mechanotransduction channel Piezo1 in osteoblastic cells impairs osteoclast activity via YAP signaling and collagen expression, leading to reduced bone mass and spontaneous fractures.

    • Lijun Wang
    • , Xiuling You
    •  & Weiguo Zou

  • Article
    | Open Access

    Exercise improves metabolic health and physical condition, particularly important for health in aged individuals. Here, the authors identify that Sestrins, proteins induced by exercise, are key mediators of the metabolic adaptation to exercise and increase endurance through the AKT and PGC1a axes.

    • Myungjin Kim
    • , Alyson Sujkowski
    •  & Jun Hee Lee

  • Article
    | Open Access

    Post-translational O-linked β-N acetylglucosamine (O-GlcNAc) modification acts as a nutrient-sensing mechanism. Here the authors report that O-GlcNAc transferase inhibits adipose tissue lipolysis via O-GlcNAcylation of the lipid droplet protein perilipin 1 and thus promotes diet-induced obesity.

    • Yunfan Yang
    • , Minnie Fu
    •  & Xiaoyong Yang

  • Article
    | Open Access

    The brain receives 20% of cardiac output, but in accord with the current knowledge lacks a specialized sensor of its own blood flow. Here, the authors show that brain astrocytes detect drops in perfusion and trigger compensatory increases in arterial pressure and heart rate to preserve brain blood flow and oxygen delivery.

    • Nephtali Marina
    • , Isabel N. Christie
    •  & Alexander V. Gourine

  • Article
    | Open Access

    Heart failure is a complex syndrome that is associated with many different underlying risk factors. Here, to increase power, the authors jointly analyse cases of heart failure of different aetiologies in a genome-wide association study and identify 11 loci of which ten had not been previously reported.

    • Sonia Shah
    • , Albert Henry
    •  & R. Thomas Lumbers

  • Article
    | Open Access

    The transcription factor DAF-16/FOXO mediates a wide variety of aging-preventive responses by driving the expression of stress resistance and longevity promoting genes. Here the authors show that transcriptional initiation at many DAF-16/FOXO target genes requires the dephosphorylation of SPT-5 by Protein Phosphatase 4.

    • Ilke Sen
    • , Xin Zhou
    •  & Christian G. Riedel

  • Article
    | Open Access

    The cellular composition of previous engineered heart tissue is often heterogeneous. Here, the authors create chamber-specific human pluripotent stem cell-derived cardiomyocytes to form both ventricular and atrial cells before embedding in collagen-based matrix to form ring-shaped engineered heart tissue.

    • Idit Goldfracht
    • , Stephanie Protze
    •  & Lior Gepstein

  • Article
    | Open Access

    Anti-resorptive bone therapies also inhibit bone formation, as osteoclasts secrete factors that stimulate bone formation by osteoblasts. Here, the authors identify osteoclast-secreted factors that couple bone resorption to bone formation in healthy subjects, and show that osteoclast-derived DPP4 may be a factor coupling bone resorption to energy metabolism.

    • Megan M. Weivoda
    • , Chee Kian Chew
    •  & Sundeep Khosla

  • Review Article
    | Open Access

    Mitochondrial metabolites contribute to more than biosynthesis, and it is clear that they influence multiple cellular functions in a variety of ways. Here, Martínez-Reyes and Chandel review key metabolites and describe their effects on processes involved in physiology and disease including chromatin dynamics, immunity, and hypoxia.

    • Inmaculada Martínez-Reyes
    •  & Navdeep S. Chandel

  • Article
    | Open Access

    Sarcopenia is the loss of muscle mass and strength associated with physical disability during ageing. Here, the authors analyse muscle biopsies from 119 patients with sarcopenia and age-matched controls of different ethnic groups and find transcriptional signatures indicating mitochondrial dysfunction, associated with reduced mitochondria numbers and lower NAD+ levels in older individuals with sarcopenia.

    • Eugenia Migliavacca
    • , Stacey K. H. Tay
    •  & Jerome N. Feige

  • Article
    | Open Access

    The edematous form of severe acute childhood malnutrition (ESAM) presents with more severe multi-organ dysfunction than non-edematous SAM (NESAM). Here the authors assess genome-wide DNA methylation in buccal cells of SAM children and find that ESAM is characterized by hypomethylation at genes associated with disorders of nutrition and metabolism, including fatty liver and diabetes.

    • Katharina V. Schulze
    • , Shanker Swaminathan
    •  & Neil A. Hanchard

  • Article
    | Open Access

    GPCRs are versatile cellular sensors for chemical stimuli but the molecular mechanisms underlying mechanically induced GPCR activation have remained elusive. Here authors identify the C-terminal helix 8 (H8) as the essential structural motif endowing H1R and other GPCRs with mechanosensitivity.

    • Serap Erdogmus
    • , Ursula Storch
    •  & Michael Mederos y Schnitzler

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