Physiology articles within Nature Communications

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  • Article
    | Open Access

    The role of the gut microbiota in hepatic lipid metabolism is controversial and incompletely understood. Here the authors perform multi-omics analyses of altered lipid metabolic processes in germ-free and specific pathogen-free mice, revealing how the gut microbiota affects hepatic fatty acid desaturation and elongation.

    • Alida Kindt
    • , Gerhard Liebisch
    •  & Josef Ecker

  • Article
    | Open Access

    Activation of integrin αIIbβ3 at the surface of platelets is required for their aggregation and for thrombus formation. Here Xu et al. identify apolipoprotein A-IV as a novel ligand for platelet αIIbβ3 integrin, and find it inhibits platelet aggregation and thrombosis.

    • Xiaohong Ruby Xu
    • , Yiming Wang
    •  & Heyu Ni

  • Article
    | Open Access

    Brown adipose tissue (BAT) thermogenesis counteracts obesity and promotes metabolic health. The role of long non-coding RNAs (lncRNAs) in the regulation of this process is not well understood. Here the authors identify a maternally expressed lncRNA, H19, that increases BAT oxidative metabolism and energy expenditure.

    • Elena Schmidt
    • , Ines Dhaouadi
    •  & Jan-Wilhelm Kornfeld

  • Article
    | Open Access

    Somatostatin+ (SOM+ ) GABAergic interneurons are known to fine-tune synaptic plasticity as they inhibit dendritic spikes and burst firing. Here, the authors show that both SOM+ and NOS+ interneurons preferentially recruit nonlinear outward-rectifying GABA(A)R with alpha5 subunit, and that this inhibition with slow gating kinetics matches voltage and time-dependent activation of synaptic NMDARs, thereby controlling the generation of dendritic NMDA spikes.

    • Jan M. Schulz
    • , Frederic Knoflach
    •  & Josef Bischofberger

  • Article
    | Open Access

    There is interest in mimicking striated muscle for a range of applications including nanomachines. Here, the authors report on synthetic 1D nanomachines which are used to study an ensemble of myosin motors interacting with an actin filament with potential to create assays of muscle related diseases

    • Irene Pertici
    • , Lorenzo Bongini
    •  & Pasquale Bianco

  • Article
    | Open Access

    The molecular mechanisms leading to heart failure in patients with Duchenne muscular dystrophy are unclear. Here the authors show that NF-κB is activated in the heart of dystrophin-deficient mice and that its ablation rescues cardiac function through chromatin remodeling and activation of gene expression.

    • Jennifer M. Peterson
    • , David J. Wang
    •  & Denis C. Guttridge

  • Article
    | Open Access

    Common genetic variants associated with plasma lipids have been extensively studied for a better understanding of common diseases. Here, the authors use whole-genome sequencing of 16,324 individuals to analyze rare variant associations and to determine their monogenic and polygenic contribution to lipid traits.

    • Pradeep Natarajan
    • , Gina M. Peloso
    •  & Sebastian Zoellner

  • Article
    | Open Access

    Ceramides are signalling molecules that regulate several physiological functions including insulin sensitivity. Here the authors report a selective ceramide synthase 1 inhibitor that counteracts lipid accumulation within the muscle and adiposity by increasing fatty acid oxidation but without affecting insulin sensitivity in mice fed with an obesogenic diet.

    • Nigel Turner
    • , Xin Ying Lim
    •  & Anthony S. Don

  • Review Article
    | Open Access

    Gut microbial metabolites are known to impact many physiological processes of the host and play a critical role in immune-homeostasis. Here the authors review our current understanding and appreciation of the importance of microbially derived tryptophan catabolites during both health and disease.

    • Henrik M. Roager
    •  & Tine R. Licht

  • Article
    | Open Access

    Dietary fatty acids have different effects on human health. Here, the authors show that ingestion of the fatty acid C18:0, but not of C16:0, rapidly leads to fusion of mitochondria and fatty acid oxidation in humans, possibly explaining the health benefits of C18:0.

    • Deniz Senyilmaz-Tiebe
    • , Daniel H. Pfaff
    •  & Aurelio A. Teleman

  • Article
    | Open Access

    Pulmonary alveolar proteinosis (PAP) is associated with defective macrophage clearance of surfactant. Here, the authors show that patients with PAP have altered cholesterol-to-phospholipid ratio in their surfactant, and that more importantly, statin therapy and reduction of cholesterol accumulation in macrophages can ameliorate PAP in both humans and mice.

    • Cormac McCarthy
    • , Elinor Lee
    •  & Bruce C. Trapnell

  • Article
    | Open Access

    Cholesterol homeostasis can modulate immunity via multiple pathways. Here the authors show that apolipoprotein E, an important regulator of cholesterol, produced by myeloid cells can regulate T cell activation by controlling the antigen presentation activity of dendritic cells in both humans and mice.

    • Fabrizia Bonacina
    • , David Coe
    •  & Giuseppe D. Norata

  • Article
    | Open Access

    Locations along the cochlea are tuned to different sound frequencies, and the individual vibration components are dynamically compressed before being converted to neural activity for further auditory processing. Here, the authors use optical coherence tomography to map sound-evoked vibrations and find a “hotspot” region with larger vibrations.

    • Nigel P. Cooper
    • , Anna Vavakou
    •  & Marcel van der Heijden

  • Article
    | Open Access

    Hypertrophic cardiomyocytes switch their metabolism from fatty acid oxidation to glucose use, but the functional role of this change is unclear. Here the authors show that high intracellular glucose inhibits the degradation of branched-chain amino acids, which is required for the activation of pro-growth mTOR signaling.

    • Dan Shao
    • , Outi Villet
    •  & Rong Tian

  • Article
    | Open Access

    Antibiotic-induced microbiome depletion is one of the most common approaches to modulate the gut microbiome. Here the authors demonstrate that it affects gut homeostasis and glucose metabolism by decreasing luminal short chain fatty acids and leading to a shift of energy utilization by colonocytes.

    • Amir Zarrinpar
    • , Amandine Chaix
    •  & Satchidananda Panda

  • Article
    | Open Access

    Circulating lipoprotein(a) is an important risk factor for cardiovascular disease and shows variability between different ethnic groups. Here, Zekavat et al. perform whole-genome sequencing in individuals of European and African ancestries and find ancestry-specific genetic determinants for lipoprotein(a) levels.

    • Seyedeh M. Zekavat
    • , Sanni Ruotsalainen
    •  & Sebastian Zoellner

  • Article
    | Open Access

    FXR plays an important role in bile acid homeostasis by transcriptionally modulating several enterohepatic genes, including intestinal FGF19, that repress hepatic bile acid synthesis. Here the authors show that postprandial FGF19 regulates FXR transcriptional activity via its action on the tyrosine kinase Src, which phosphorylates FXR.

    • Sangwon Byun
    • , Dong-Hyun Kim
    •  & Jongsook Kim Kemper

  • Article
    | Open Access

    Human embryonic stem cell-derived cardiomyocytes (hESC-CM) are a widely used model to study cardiac genomics. Here, Choy et al. perform promoter capture Hi-C to map long-range chromosomal interactions of hESC-CMs and to study overlap of such regions with genetic loci associated with cardiac phenotypes.

    • Mun-Kit Choy
    • , Biola M. Javierre
    •  & Bernard D. Keavney

  • Article
    | Open Access

    The transcription factor FOXA2 is specifically expressed in uterine glands. Here, using two conditional FOXA2 knockout mouse models, the authors show that glandular epithelia of the endometrium are required for timely embryo implantation and subsequent endometrial decidualization during successful pregnancy establishment.

    • Andrew M. Kelleher
    • , Jessica Milano-Foster
    •  & Thomas E. Spencer

  • Article
    | Open Access

    During atherosclerosis, endothelial cells release purines in response to oxidized phospholipids. Here, Hitzel et al. show that oxidized phospholipids activate an MTHFD2-regulated gene network in endothelial cells which reprograms amino acid metabolism towards production of purines and thus compensates for their loss.

    • Juliane Hitzel
    • , Eunjee Lee
    •  & Ralf P. Brandes

  • Article
    | Open Access

    Osmotic forces do not suffice to explain the rate of cerebrospinal fluid (CSF) production. Here, the authors show that the Na+/K+/2Cl− cotransporter in the choroid plexus contributes substantially to CSF production via its inherent ability to cotransport water.

    • Annette B. Steffensen
    • , Eva K. Oernbo
    •  & Nanna MacAulay

  • Article
    | Open Access

    Hepatic fibrosis represents the liver response to chronic injury and can lead to cirrhosis. Here the authors show that mucosal-associated invariant T cells mediate chronic inflammation and fibrogenesis in the liver by inducing a proinflammatory phenotype in macrophages and myofibroblasts and proliferation of the latter.

    • Pushpa Hegde
    • , Emmanuel Weiss
    •  & Sophie Lotersztajn

  • Article
    | Open Access

    Hyperinsulinemia can precede the development of insulin resistance. Here the authors identify a PKD2 mutation that leads to hyperinsulinemia and insulin resistance in Rhesus monkey and show that PKD2 deficiency promotes beta cell insulin secretion by activating L-type Ca2+ channels.

    • Yao Xiao
    • , Can Wang
    •  & Xiuqin Zhang

  • Article
    | Open Access

    Late-differentiating second heart field progenitors contribute to atrium, ventricle, and outflow tract in the zebrafish heart but how remains unclear. Here, the authors image heart formation in transgenics based on the cardiopharyngeal gene tbx1 and show that progenitors are continuously added.

    • Anastasia Felker
    • , Karin D. Prummel
    •  & Christian Mosimann

  • Article
    | Open Access

    Insulin secretion by β-cells is stimulated by glucose and is dependent on the induction of β-cell membrane depolarization, mainly driven by the closure of KATP channels, which in turn promotes voltage-gated Ca2+ channel opening. Here the authors show that LRRC8 volume-regulated anion channels (VRACs) modulate glucose-stimulated calcium increase and insulin secretion.

    • Till Stuhlmann
    • , Rosa Planells-Cases
    •  & Thomas J. Jentsch

  • Article
    | Open Access

    Genome-wide association studies have identified multiple loci for resting heart rate (HR) but the genetic factors associated with HR increase during and HR recovery after exercise are less well studied. Here, the authors examine both traits in a two-stage GWAS design in up to 67,257 individuals from UK Biobank.

    • Julia Ramírez
    • , Stefan van Duijvenboden
    •  & Patricia B. Munroe

  • Article
    | Open Access

    M-current is conveyed by voltage-sensitive KCNQ channels, which are enriched in GABAergic neurons and are activated by anticonvulsants such as retigabine. Here the authors show that GABA directly activates KCNQ3, at the residue required for its anticonvulsant activity.

    • Rían W. Manville
    • , Maria Papanikolaou
    •  & Geoffrey W. Abbott

  • Article
    | Open Access

    Non-invasive techniques to assess the progression of type 1 diabetes prior to clinical onset are needed. Here the authors apply a contrast-enhanced ultrasound measurement of mouse pancreatic blood flow to detect changes in the islet microvasculature that undergoes rearrangements during diabetes and predict disease progression.

    • Joshua R. St Clair
    • , David Ramirez
    •  & Richard K. P. Benninger

  • Article
    | Open Access

    Hutchinson-Gilford Progeria Syndrome is characterized by premature aging with cardiovascular disease being the main cause of death. Here the authors show that inhibition of the NAT10 enzyme enhances cardiac function and fitness, and reduces age-related phenotypes in a mouse model of premature aging.

    • Gabriel Balmus
    • , Delphine Larrieu
    •  & Stephen P. Jackson

  • Article
    | Open Access

    GPR40 is a G-protein coupled receptor that binds to free fatty acids, mediating insulin and incretin secretion. Here, the authors present the crystal structure of human GPR40 with an agonist bound to an allosteric site located near the lipid-rich region that suggests a mechanism for biased agonism.

    • Joseph D. Ho
    • , Betty Chau
    •  & Chafiq Hamdouchi

  • Article
    | Open Access

    As a circadian organ, liver functions are regulated by circadian clock. Here, the authors present a comprehensive proteomics landscape of the mouse liver, including transcription factor binding profiles, phosphorylation and ubiquitylation patterns, nuclear and whole proteome, and the transcriptome.

    • Yunzhi Wang
    • , Lei Song
    •  & Chen Ding

  • Article
    | Open Access

    JMJD1A is essential for thermogenic gene induction in brown adipose tissue. Here the authors show that white adipose tissue beige-ing requires both β-adrenergic-dependent phosphorylation of S265 and demethylation activity of JMJD1A while brown adipose tissue-driven thermogenesis requires β-adrenergic dependent phosphorylation of S265 but is independent of H3K9me2 demethylation.

    • Yohei Abe
    • , Yosuke Fujiwara
    •  & Juro Sakai

  • Article
    | Open Access

    Sexual dimorphism exists in a number of physiological processes, including energy homeostasis. Here, the authors show that pro-opiomelanocortin neurons in female mice fire more rapidly than males, and that deletion of the transcription TAp63 leads to a reduced neuronal firing rate and a male-like susceptibility to diet-induced obesity.

    • Chunmei Wang
    • , Yanlin He
    •  & Yong Xu

  • Article
    | Open Access

    Cathelicidins are antimicrobial peptides that eliminate pathogens and contribute to the innate immune response. Here the authors show that neutrophil-derived LL-37/CRAMP induces platelet activation and promotes arterial thrombosis and thrombo-inflammation.

    • Joachim Pircher
    • , Thomas Czermak
    •  & Christian Schulz

  • Article
    | Open Access

    Iron homeostasis dysfunctions have been associated with several metabolic disorders including obesity, steatosis and diabetes. Here the authors demonstrate that the hepcidin repressor matriptase-2 regulates adiposity and its deficiency protects mice against obesity and promotes lipolysis.

    • Alicia R. Folgueras
    • , Sandra Freitas-Rodríguez
    •  & Carlos López-Otín

  • Article
    | Open Access

    A gene regulatory network, including the transcription factor Nkx2-5, regulates cardiac development. Here, the authors show that on deletion of NKX2-5 from human embryonic stem cells, there is impaired cardiomyogenesis and changes in action potentials, and that this is regulated via HEY2.

    • David J. Anderson
    • , David I. Kaplan
    •  & David A. Elliott

  • Article
    | Open Access

    Declining NAD+ levels have been linked to aging-associated pathologies. Here the authors present results of a double-blind, randomized crossover trial on 30 healthy middle-aged individuals to show that nicotinamide riboside effectively elevates NAD+ levels in humans, appears to be well tolerated, and may have potential to improve cardiovascular parameters.

    • Christopher R. Martens
    • , Blair A. Denman
    •  & Douglas R. Seals

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