Physiology articles within Nature Communications

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  • Article
    | Open Access

    IL11 contributes to the development of non-alcoholic steatohepatitis (NASH) through incompletely understood mechanisms. Here, the authors report that lipotoxicity-driven autocrine IL11 activity underlies hepatocyte metabolic dysfunction and death via a NOX4/ERK-mediated mechanism while paracrine IL11 activity stimulates hepatic stellate cells contributing to fibrosis and inflammation in the context of NASH.

    • Jinrui Dong
    • , Sivakumar Viswanathan
    •  & Anissa A. Widjaja

  • Article
    | Open Access

    Torpor is a state of reduced metabolism and body temperature that conserves energy when food is scarce. Here the authors show that estrogen-sensitive neurons in the hypothalamus regulate torpor in mice, maintaining torpor in both sexes but initiating torpor and regulating core temperature differentially across sex.

    • Zhi Zhang
    • , Fernando M. C. V. Reis
    •  & Stephanie M. Correa

  • Article
    | Open Access

    Therapeutic angiogenesis has the potential of inducing and maintaining new blood vessels and thus improving outcomes in patients with ischemic disorders. Mannosamine functions as an endothelial cell mitogen/survival factor through activation of stress pathways and might be useful to protect and regenerate the vascular endothelium in a variety of disorders.

    • Cuiling Zhong
    • , Pin Li
    •  & Napoleone Ferrara

  • Article
    | Open Access

    Hypothalamic melanocortin neurons regulate systemic glucose homeostasis through incompletely understood pathways. Here, the authors show that a subset of pro-opiomelanocortin neurons innervate the liver via preganglionic parasympathetic cholinergic neurons in the dorsal motor nucleus of the vagus and that stimulation of this pathway elevates blood glucose levels

    • Eunjin Kwon
    • , Hye-Young Joung
    •  & Young-Hwan Jo

  • Article
    | Open Access

    The in vivo firing patterns of ventral midbrain dopamine neurons are controlled by afferent and intrinsic activity. The authors identified biophysical membrane potential signatures associated with distinct in vivo firing patterns in whole-cell recordings of spontaneously active midbrain dopamine neurons.

    • Kanako Otomo
    • , Jessica Perkins
    •  & Carlos A. Paladini

  • Article
    | Open Access

    To be successful, selective neuromodulation requires a non-invasive method of imaging the fascicular anatomy of peripheral nerves. Here, the authors show the applicability and reliability of fast neural electrical impedance tomography for this purpose and provide its validation against the gold standards of invasive imaging.

    • Enrico Ravagli
    • , Svetlana Mastitskaya
    •  & David Holder

  • Article
    | Open Access

    Current therapeutic strategies for vitamin D-induced hypercalcemia are poorly efficient. Here the authors identify a new interaction between the vitamin D receptor (VDR) and WBP4 controlling the subcellular localization of VDR and show that ZK168281, a VDR antagonist, enhances the interaction between VDR and WBP4 blunting VDR signalling and normalizing calcium levels in vitamin D-intoxicated mice.

    • Daniela Rovito
    • , Anna Y. Belorusova
    •  & Daniel Metzger

  • Article
    | Open Access

    Hepatocyte 12-hour rhythms have a role in cellular stress and metabolic functions. Here, the authors demonstrate disrupting the 12-hour clock through deletion of XBP1 is associated with the development of NAFLD as well as disruption of phospholipid composition and the maintenance of lipid homeostasis.

    • Huan Meng
    • , Naomi M. Gonzales
    •  & Bert W. O’Malley

  • Article
    | Open Access

    Theta and gamma rhythms are essential to ensure timely communication between brain structures during locomotion. Here the authors investigate the association between cerebral blood flow and neural oscillations in freely behaving mice running a linear track.

    • Antoine Bergel
    • , Elodie Tiran
    •  & Ivan Cohen

  • Article
    | Open Access

    Maintenance of a mitochondrial NAD+ pool is critical for cellular life, yet the existence and identity of the transporter responsible for mitochondrial NAD+ uptake was unknown until recently. Here, the authors use genomic, genetic, and metabolomic approaches to demonstrate that SLC25A51 controls NAD+ mitochondrial levels and is the functional homolog of the yeast mitochondrial NAD+ transporter.

    • Enrico Girardi
    • , Gennaro Agrimi
    •  & Giulio Superti-Furga

  • Article
    | Open Access

    Excessive glucose production by the liver contributes to poor blood glucose control in type 2 diabetes. Here the authors report that the liver kinase B1 (Lkb1) suppresses amino acid driven postprandial glucose production in the liver through the aminotransferase Agxt.

    • Pierre-Alexandre Just
    • , Sara Charawi
    •  & Christine Perret

  • Comment
    | Open Access

    Extreme heat adversely affects human health, productivity, and well-being, with more frequent and intense heatwaves projected to increase exposures. However, current risk projections oversimplify critical inter-individual factors of human thermoregulation, resulting in unreliable and unrealistic estimates of future adverse health outcomes.

    • Jennifer K. Vanos
    • , Jane W. Baldwin
    •  & Kristie L. Ebi

  • Article
    | Open Access

    Monitoring hemodynamics in the brain is important in understanding medical imaging data and mechanisms of disease. Here the authors use high-throughput two-photon microscopy with an axially-extended Bessel focus to measure vessel size and blood flow down to capillary scale in the awake mouse brain.

    • Jiang Lan Fan
    • , Jose A. Rivera
    •  & Na Ji

  • Article
    | Open Access

    The proliferation of pancreatic beta cells decreases with age, partly due to systemic changes. Here the authors identify Wisp1 as a circulating factor enriched in young serum that induces adult beta cell proliferation, supporting the idea that young blood factors may be useful to expand beta cell mass.

    • Rebeca Fernandez-Ruiz
    • , Ainhoa García-Alamán
    •  & Rosa Gasa

  • Article
    | Open Access

    Organismal metabolism fluctuates depending on nutritional conditions. Here, the authors show that, in C. elegans, HLH-11 negatively regulates lipid metabolism genes in the presence of nutrients and that its abundance decreased in response to starvation, thereby promoting fat utilization.

    • Yi Li
    • , Wanqiu Ding
    •  & Ying Liu

  • Article
    | Open Access

    Hepatic lipogenesis is a tightly regulated process, which is elevated in obesity. Here the authors report that FGF15/19, bile acid-induced gut hormones, repress lipogenic genes in the late fed-state by activating small heterodimer partner (SHP) and promoting SHP-dependent recruitment of DNA methyltransferase DNMT3A to lipogenic genes.

    • Young-Chae Kim
    • , Sunmi Seok
    •  & Jongsook Kim Kemper

  • Article
    | Open Access

    Skeletal muscle plays a key role in regulating systemic glucose and metabolic homeostasis. Here, the authors show that the catalytic activity of Vav2, an activator of Rho GTPases, modulates those processes by favoring the responsiveness of this tissue to insulin and related factors.

    • Sonia Rodríguez-Fdez
    • , L. Francisco Lorenzo-Martín
    •  & Xosé R. Bustelo

  • Article
    | Open Access

    Breakdown of vascular barriers is a major complication of inflammatory diseases. However, the mechanisms underlying platelet recruitment to inflammatory micro-environments remains unclear. Here, the authors identify haptotaxis as a key effector function of immune-responsive platelets

    • Leo Nicolai
    • , Karin Schiefelbein
    •  & Florian Gaertner

  • Article
    | Open Access

    Neurofibromatosis type I (NF1) is characterized by prominent skeletal abnormalities mediated in part by aberrant ERK pathway activation due to NF1 loss-of-function. Here, the authors report the MEKK2 is a key mediator of this aberrant ERK activation and that MEKK2 inhibitors, including ponatinib, ameliorate skeletal defects in a mouse model of NF1.

    • Seoyeon Bok
    • , Dong Yeon Shin
    •  & Matthew B. Greenblatt

  • Article
    | Open Access

    Circular RNAs contribute to the regulation of β-cell specific functions. Here the authors show that a circular RNA derived from one of the introns of the insulin gene is necessary for optimal insulin secretion from pancreatic islets and that its level is reduced in the islets of diabetic subjects.

    • Lisa Stoll
    • , Adriana Rodríguez-Trejo
    •  & Romano Regazzi

  • Article
    | Open Access

    Current media for neuronal cell and organoid cultures are suboptimal for functional imaging and optogenetics experiments, owing to phototoxicity and unphysiological performance. Here the authors formulate an optimised neuronal medium to support live cell imaging and electrophysiological activity.

    • Michael Zabolocki
    • , Kasandra McCormack
    •  & Cedric Bardy

  • Article
    | Open Access

    The expansion of the white adipose tissue during obesity is accompanied by increased cellular stress, but factors that protect adipocytes from cell death are not well known. Here the authors report that the transcriptional co-activators YAP and TAZ are activated in adipocytes during obesity, which increases adipocyte survival through the proapoptotic factor BIM.

    • Lei Wang
    • , ShengPeng Wang
    •  & Stefan Offermanns

  • Article
    | Open Access

    GABAA receptors mediate most inhibitory synaptic transmission in the brain. Here authors used concatemeric α1β2γ2 GABAA receptors to introduce gain-of-desensitization mutations one subunit at a time, revealing non-concerted rearrangements with a key contribution of the γ2 subunit during desensitization.

    • Marc Gielen
    • , Nathalie Barilone
    •  & Pierre-Jean Corringer

  • Article
    | Open Access

    Molecular mechanisms by which glucose modulates L-type Ca2+ channel activity and vascular reactivity are unclear. Here the authors report a nanocomplex orchestrated by AKAP5 that facilitates local purinergic stimulation of L-type Ca2+ channels and vasoconstriction during diabetic hyperglycemia.

    • Maria Paz Prada
    • , Arsalan U. Syed
    •  & Madeline Nieves-Cintrón

  • Article
    | Open Access

    Social interactions require monitoring others’ actions to optimally organise one’s own actions. Here, the authors show that the pathway from the ventral premotor cortex (PMv) to the medial prefrontal cortex (MPFC) is causally involved in monitoring observed, but not executed, actions.

    • Taihei Ninomiya
    • , Atsushi Noritake
    •  & Masaki Isoda

  • Article
    | Open Access

    Clinical neuroprotective strategies for acute spinal cord injury (SCI) have largely overlooked the heart. Here the authors show cardiac contractility is immediately impaired in a porcine model of T2 SCI, and cardio-centric treatment with dobutamine optimizes cord oxygenation and mitigates haemorrhage.

    • Alexandra M. Williams
    • , Neda Manouchehri
    •  & Christopher R. West

  • Article
    | Open Access

    Leptin treatment is effective to reduce body weight in animal models, but patients with obesity and associated hyperleptinemia do not respond well to leptin therapy. Here the authors report a retrospective analysis of four clinical trials in normo- and mildly hypoleptinemic individuals and show that leptin therapy alters food intake in the short term and reduces weight and fat mass in the long term without effects on energy expenditure.

    • Pavlina Chrysafi
    • , Nikolaos Perakakis
    •  & Christos S. Mantzoros

  • Article
    | Open Access

    There are several pathways for CO2 fixation in photoautotrophic and chemoautotrophic microorganisms. Here, the authors provide experimental demonstration for the operation of the reductive glycine pathway in a natural microorganism, Desulfovibrio desulfuricans.

    • Irene Sánchez-Andrea
    • , Iame Alves Guedes
    •  & Alfons J. M. Stams

  • Article
    | Open Access

    Laboratory performance tests provide the gold standard for running performance but do not reflect real running conditions. Here the authors use a large, real world dataset obtained from wearable exercise trackers to extract parameters that accurately predict race times and correlate with training.

    • Thorsten Emig
    •  & Jussi Peltonen

  • Article
    | Open Access

    Necrotizing enterocolitis (NEC) is one of the most lethal gastrointestinal emergencies in neonates needing precision treatment. Here the authors show that remote ischemic conditioning is a non-invasive therapeutic method that enhances blood flow in the intestine, reduces damage, and improves NEC outcome.

    • Yuhki Koike
    • , Bo Li
    •  & Agostino Pierro

  • Article
    | Open Access

    Early stages of the novel coronavirus disease (COVID-19) have been associated with silent hypoxia and poor oxygenation despite relatively small fractions of afflicted lung. Here, the authors present a mathematical model which reproduces the vascular pulmonary mechanisms observed in patients with early COVID-19.

    • Jacob Herrmann
    • , Vitor Mori
    •  & Béla Suki

  • Article
    | Open Access

    Myeloid cells are involved in hypertension, but their exact role in renin-induced hypertension remains unclear. Here the authors show that impaired vitamin D signaling in myeloid cells causes hypertension via macrophage-specific miR-106b-5p secretion, which activates renin production in the kidney.

    • J. Oh
    • , S. J. Matkovich
    •  & C. Bernal-Mizrachi

  • Article
    | Open Access

    Intercalated discs ensure mechanical and electrochemical coupling during contraction of the heart. Here, the authors show that loss of Xinβ results in cardiomyocyte proliferation defects and cardiomyopathy by influencing the Hippo-YAP signalling pathway, thus affecting cardiac development and function.

    • Haipeng Guo
    • , Yao Wei Lu
    •  & Da-Zhi Wang

  • Article
    | Open Access

    The discovery of interventions that slow aging could be accelerated by employing non-invasive biometrics that predict biological age or life expectancy. Here the authors use longitudinal frailty data from naturally aging mice to develop two such tools, that are responsive to interventions.

    • Michael B. Schultz
    • , Alice E. Kane
    •  & David A. Sinclair

  • Article
    | Open Access

    mTORC1 expression is increased during ageing of muscle, and on the other hand, its activation promotes muscle hypertrophy. Here, the authors assess whether mTORC1 has positive or negative effects on ageing, and show that its long-term inhibition preserves muscle mass and function and neuromuscular junction integrity, whereas muscle-specific activation is associated with sarcopenia.

    • Daniel J. Ham
    • , Anastasiya Börsch
    •  & Markus A. Rüegg

  • Article
    | Open Access

    Little is known about how cardiac metabolism remodels following cardiac injury. Here, the authors show that mitochondrial CaMKII plays an important role in remodeling cardiac metabolism after injury and that replacement of mitochondrial creatine kinase improves energetics and protects against adverse remodeling.

    • Elizabeth D. Luczak
    • , Yuejin Wu
    •  & Mark E. Anderson

  • Article
    | Open Access

    Blood–brain barrier dysfunction occurs in ageing and in neurodegenerative diseases. Here, the authors use scRNA-seq to identify transcriptomic changes in endothelial cell subtypes in the aged mouse brain, some of which may generalize to human and can be reversed by treatment with a GLP-1R agonist.

    • Lei Zhao
    • , Zhongqi Li
    •  & Ho Ko

  • Article
    | Open Access

    How the developmental capacity of long-lived animals copes with fluctuations in the food supply is unclear. Here, the authors show using the sea anemone Nematostella vectensis that the crosstalk between Target of Rapamycin and fibroblast growth factor signalling in ring muscles links postembryonic tentacle patterning with food availability.

    • Aissam Ikmi
    • , Petrus J. Steenbergen
    •  & Matthew C. Gibson

  • Article
    | Open Access

    Salt levels in culture affect the polarisation of Th17 cells, which normally protect the host from fungal and bacterial infections. Here, the authors study patients with salt-losing tubulopathies (SLT) to find that, while Th17 immunity is dampened in SLT patients, their Th17-inducing signaling pathways are intact and can be reinvigorated by exogenous salt.

    • Rhys D. R. Evans
    • , Marilina Antonelou
    •  & Alan D. Salama

  • Article
    | Open Access

    The failing heart is characterised by both alterations in mitochondrial metabolism and an elevation of cytosolic sodium. Here, the authors use 23Na NMR and metabolic profiling to show these are related, and that elevation in intracellular Na reprograms cardiac substrate utilisation via effects on mitochondrial Na/Ca exchange.

    • Dunja Aksentijević
    • , Anja Karlstaedt
    •  & Michael J. Shattock

  • Article
    | Open Access

    Ketamine is a general anesthetic that is used also as an anti-depressant, but its use is associated with cystitis. Here, the authors show that ketamine is an antagonist of the Cav1.2 channel in bladder smooth muscle cells, that ablation of this channel in mice mimics the cystitis induced by ketamine, and show that this effect can be abrogated by an agonist of this ion channel.

    • Huan Chen
    • , David H. Vandorpe
    •  & Weiqun Yu

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