Physiology articles within Nature Communications

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  • Article
    | Open Access

    Reduction in food intake elicits neuroendocrine adaptations to counterregulate the negative energy balance, e.g. via reduction in leptin levels. Here, the authors identify an additional starvation signal, growth hormone (GH). Blocking GH receptor attenuates the fall of whole body energy expenditure during food deprivation in mice.

    • Isadora C. Furigo
    • , Pryscila D. S. Teixeira
    •  & J. Donato Jr

  • Article
    | Open Access

    Insulin-related gene (Insig) negatively regulates hepatic fatty acid synthesis, a process involved in development of non-alcoholic fatty liver disease (NAFLD). Here, the authors show that AMPK activation by metformin promotes Insig phosphorylation, stabilizing it and inhibiting lipogenic gene expression. This is protective against steatosis in diabetic mice.

    • Yamei Han
    • , Zhimin Hu
    •  & Yu Li

  • Article
    | Open Access

    The use of pluripotent-stem cell derived organs for transplantation would be promising, if organs can be grown in a suitable host. Here, the authors use interspecific blastocyst complementation to generate a mouse pluripotent stem cell-derived kidney in anephric Sall1 mutant rats.

    • Teppei Goto
    • , Hiromasa Hara
    •  & Masumi Hirabayashi

  • Article
    | Open Access

    Heart grafts need good vascularization to survive. Here, the authors engineer perfusable constructs of human embryonic stem cell-derived endothelial cells seeded in collagen matrix in patterned microchannels that form anastomosed vessels in vitro and have increased coronary vascular perfusion on transplantation in rats.

    • Meredith A. Redd
    • , Nicole Zeinstra
    •  & Ying Zheng

  • Article
    | Open Access

    The use of sodium-glucose transport protein 2 (SGLT2) inhibitors for the treatment of diabetes has been associated with euglycemic ketoacidosis and increased glucose production and glucagon secretion. Here Perry et al. show that these effects rely on both insulinopenia and dehydration, and thus suggest ways to manage the side effects associated with the use of SGLT2 inhibitors.

    • Rachel J. Perry
    • , Aviva Rabin-Court
    •  & Gerald I. Shulman

  • Article
    | Open Access

    Individuals show large variability in their capacity to lose weight and maintain this weight. Here, the authors perform GWAS in two weight loss intervention cohorts and identify two genetic loci associated with weight loss that are taken forward for Bayesian fine-mapping and functional assessment in flies.

    • Armand Valsesia
    • , Qiao-Ping Wang
    •  & Jörg Hager

  • Article
    | Open Access

    Metabolic pathways are increasingly recognized as crucial determinants of T cell function. Here the authors show that the balance between IFNγ and IL-10 production in human CD4 T cells is modulated by the cholesterol biosynthetic pathway.

    • Esperanza Perucha
    • , Rossella Melchiotti
    •  & Andrew P. Cope

  • Article
    | Open Access

    Obesity is associated with altered N-acylethanolamine levels (NAE). Here the authors show that deletion of the gene encoding N-acylphosphatidylethanolamine phospholipase D, a key enzyme for NAE synthesis, in intestinal cells of mice leads to the development of obesity and hepatic steatosis via a mechanism involving the gut-brain axis.

    • Amandine Everard
    • , Hubert Plovier
    •  & Patrice D. Cani

  • Article
    | Open Access

    In atherosclerotic plaques, transformation of macrophages into foam cells is a key step in initiating the inflammatory response. Here Fan et al. show that casein kinase 2-interacting protein-1 (CKIP-1) limits foam cell formation and atherosclerosis by preventing expression of the scavenger receptor LOX-1 through REGγ-mediated degradation of Oct-1.

    • Jiao Fan
    • , Lifeng Liu
    •  & Lingqiang Zhang

  • Article
    | Open Access

    Obesity and the distribution of fat within the body are risk factors for cardiometabolic diseases. Here, Rask-Andersen et al. perform GWAS for bio-electrical impedance measurements in UK Biobank participants and identify 29 novel independent loci for fat distribution and a high degree of sex-heterogeneity.

    • Mathias Rask-Andersen
    • , Torgny Karlsson
    •  & Åsa Johansson

  • Article
    | Open Access

    Agouti-related peptide (AgRP) producing neurons regulate food intake and metabolic processes in peripheral organs. Here, the authors show that hypothalamic AgRP neurons alter whole body substrate utilization to favour carbohydrate usage and lipid storage.

    • João Paulo Cavalcanti-de-Albuquerque
    • , Jeremy Bober
    •  & Marcelo O. Dietrich

  • Article
    | Open Access

    Bone is innervated, and its turnover is affected by sympathetic nerve activity. Here, the authors show that prostaglandin E2, secreted by osteoblasts, activates the EP4 receptor on sensory nerves, inhibiting sympathetic nerve activity and modulating bone formation in mice.

    • Hao Chen
    • , Bo Hu
    •  & Xu Cao

  • Article
    | Open Access

    Imbalanced proteostasis is associated with diverse diseases, including ischemia/reperfusion injury in the heart. Here the authors show that the ATF6 arm of the unfolded protein response can be pharmacologically activated with a small molecule in vivo, providing protection from ischemia/reperfusion injury in the heart, the brain, and the kidney.

    • Erik A. Blackwood
    • , Khalid Azizi
    •  & Christopher C. Glembotski

  • Article
    | Open Access

    Impaired glucagon secretion in patients with diabetes causes hypoglycemia. Here the authors show that therapeutic concentrations of insulin inhibit alpha-cell glucagon secretion by stimulating delta-cell insulin receptor and the release of somatostatin. Blocking somatostatin secretion or action ameliorates this effect.

    • Elisa Vergari
    • , Jakob G. Knudsen
    •  & Patrik Rorsman

  • Article
    | Open Access

    Estrogen promotes negative energy balance and preserves skeletal physiology. Here the authors show that loss of estrogen signalling after ablating estrogen receptor alpha (ERa) in specific hypothalamic neuronal populations leads to a marked sex-dependent increase in bone mass in female mice.

    • Candice B. Herber
    • , William C. Krause
    •  & Holly A. Ingraham

  • Article
    | Open Access

    Nephrogenesis ceases after postnatal day 2 in the mouse or after the 36th week of gestation in humans, but how this is regulated is unclear. Here, the authors identify a role for the RNA-binding protein Lin28 and suppression of let-7 microRNA in regulating the duration of nephrogenesis.

    • Alena V. Yermalovich
    • , Jihan K. Osborne
    •  & George Q. Daley

  • Article
    | Open Access

    The Ca2+-activated Cl- channel TMEM16A/Anoctamin 1 (ANO1) mediates secretion and intestinal motility in gastrointestinal epithelia and smooth muscle cells. Here, the authors show a role for ANO1 in zebrafish skeletal muscle which is activated by SR Ca2+ release during excitation-contraction coupling.

    • Anamika Dayal
    • , Shu Fun J. Ng
    •  & Manfred Grabner

  • Article
    | Open Access

    While human lifespan is only moderately heritable, “getting old” runs in families. Here, van den Berg et al. study mortality data from three-generation cohorts to define a threshold for longevity and find that individuals have an increasing survival advantage with each additional relative in the top 10% survivors of their birth cohort.

    • Niels van den Berg
    • , Mar Rodríguez-Girondo
    •  & P. Eline Slagboom

  • Article
    | Open Access

    The mechanisms underlying the regenerative capacity of the liver are not fully understood. Here, the authors show that the acute regenerative response to liver injury in mice is regulated by the communication involving the vagus nerve, macrophages, and hepatocytes, leading to hepatic FoxM1 activation and promotion of overall survival.

    • Tomohito Izumi
    • , Junta Imai
    •  & Hideki Katagiri

  • Article
    | Open Access

    Understanding the pH changes at cell surfaces is important for understanding the mechanisms of different physiological processes. Here, the authors report on the development of a cell membrane anchored gold nanoparticle for surface enhanced Raman spectroscopy determination of pH.

    • Leonardo Puppulin
    • , Shigekuni Hosogi
    •  & Yoshinori Marunaka

  • Article
    | Open Access

    The molecular pathway(s) driving antipsychotics (AP) induced hyperphagia remains unclear. A novel C. elegans system is used here to screen for FDA approved drugs that selectively suppresses this response, unraveling potential molecular mediators influencing AP induced hyperphagia in mouse models.

    • Anabel Perez-Gomez
    • , Maria Carretero
    •  & Michael Petrascheck

  • Article
    | Open Access

    VEGF-C drives lymphangiogenesis through binding to its receptors VEGFR-2 and VEGFR-3. Here, Durré et al. identify uPARAP/Endo180 as a critical regulator of VEGFR-2/VEGFR-3 heterodimerisation and downstream signaling in response to VEGF-C, and show that uPARAP deletion leads to the formation of hyperbranched vasculatures in pathological conditions.

    • Tania Durré
    • , Florent Morfoisse
    •  & Agnès Noel

  • Article
    | Open Access

    Carotid intima-media thickness (cIMT) and plaque are associated with subclinical atherosclerosis and coronary heart disease (CHD). Here, the authors identify and prioritize genetic loci for cIMT and plaque by GWAS and colocalization approaches and further demonstrate genetic correlation with CHD and stroke.

    • Nora Franceschini
    • , Claudia Giambartolomei
    •  & Christopher J. O’Donnell

  • Article
    | Open Access

    Endocannabinoid signaling regulates food intake and is a potential therapeutic target for obesity. Here the authors show that adipocyte O-GlcNAc transferase (OGT) is required for high fat diet-induced hyperphagia via transcriptional activation of de novo lipid desaturation and accumulation of an endogenous appetite-inducing cannabinoid.

    • Min-Dian Li
    • , Nicholas B. Vera
    •  & Xiaoyong Yang

  • Article
    | Open Access

    Assessing biological circuit connections in single cells has been intractable due to lack of appropriate tools. Here, Bleck et al. develop a method to assess mitochondrial network connectivity in muscle cells and observe clear differences consistent with differing energy requirements.

    • Christopher K. E. Bleck
    • , Yuho Kim
    •  & Brian Glancy

  • Review Article
    | Open Access

    Transcranial electrical stimulation techniques, such as tDCS and tACS, are popular tools for neuroscience and clinical therapy, but how low-intensity current might modulate brain activity remains unclear. In this review, the authors review the evidence on mechanisms of transcranial electrical stimulation.

    • Anli Liu
    • , Mihály Vöröslakos
    •  & György Buzsáki

  • Article
    | Open Access

    The mechanisms that regulate the activity of Ca2 +/calmodulin-dependent protein kinase II (CaMKII) in the context of heart failure are incompletely understood. Here the authors show that protein arginine methyltransferase 1 (PRMT1) prevents cardiac hyperactivation of CaMKII and heart failure development by methylating CaMKII at arginine residues 9 and 275.

    • Jung-Hoon Pyun
    • , Hyun-Ji Kim
    •  & Jong-Sun Kang

  • Article
    | Open Access

    Long-range GABAergic hippocampal neurons project to cortical and subcortical areas, while vasoactive intestinal peptide (VIP+) interneurons can inhibit other GABAergic neurons. Here, authors discover a VIP+, long-range projecting GABAergic neuron whose activity is associated with quiet wakefulness.

    • Ruggiero Francavilla
    • , Vincent Villette
    •  & Lisa Topolnik

  • Article
    | Open Access

    Blood pressure (BP) is a major risk factor for cardiovascular disease and more than 200 genetic loci associated with BP are known. Here, the authors perform discovery GWAS for BP in East Asians and meta-analysis in East Asians and Europeans and report ancestry-specific BP SNPs and selection signals.

    • Fumihiko Takeuchi
    • , Masato Akiyama
    •  & Norihiro Kato

  • Article
    | Open Access

    Respiratory failure is one of the leading causes of death following spinal cord injury and it is unclear if normal respiratory motor activity can be recovered after chronic injury-induced paralysis. Here, authors show that treatment with chondroitinase ABC induces robust rescue of breathing up to 1.5 years following complete hemidiaphragm paralysis.

    • Philippa M. Warren
    • , Stephanie C. Steiger
    •  & Jerry Silver

  • Article
    | Open Access

    The molecular mechanisms that underlie associations in GWAS, incl. chronic kidney disease (CKD), are largely unknown. Here, the authors perform an integrative analysis of genetic, transcriptomic and epigenomic data from human kidney to pinpoint plausible molecular pathways of CKD genetic associations.

    • Xiaoguang Xu
    • , James M. Eales
    •  & Maciej Tomaszewski

  • Article
    | Open Access

    While autapses are synapses made by a neuron onto itself, its functional significance in pyramidal cells are not clear. Here, the authors show that in the mammalian neocortex, autapses of pyramidal cells can enhance burst firing and coincidence detection from other inputs.

    • Luping Yin
    • , Rui Zheng
    •  & Yousheng Shu

  • Article
    | Open Access

    While young muscle faithfully regenerates damaged myofibers, aged muscle is impaired. Here the authors show the “anti-aging” protein α-Klotho is upregulated in young muscle after damage via promoter demethylation and this regulation is lost in aging, resulting in mitochondrial damage and an impaired healing response.

    • A. Sahu
    • , H. Mamiya
    •  & F. Ambrosio

  • Article
    | Open Access

    No effective pharmacological treatments exist for nonalcoholic fatty liver disease (NAFLD). Here, the authors show that serotonin concentration in the portal blood is increased in nine human subjects and in mice fed a high-fat diet, and that local serotonin signaling ablation, either genetically or with an antagonist, prevents hepatic steatosis in mice.

    • Wonsuk Choi
    • , Jun Namkung
    •  & Hail Kim

  • Article
    | Open Access

    Angiogenesis requires dynamic endothelial rearrangements and relative position changes within the vascular tubes. Here the authors show that a PI3K/NUAK1/MYPT1/MLCP pathway regulates actomyosin contractility in endothelial cells and cellular rearrangement during vascular patterning.

    • Ana Angulo-Urarte
    • , Pedro Casado
    •  & Mariona Graupera

  • Article
    | Open Access

    Constitutive deletion of Rcan1 has been previously shown to prevent Angiotensin II-induced aneurysm in mice. Here the authors show that tissue-specific inducible deletion of Rcan1 in vascular cell types predisposes to hypertension-mediated aortic rupture, intramural hematoma, and aneurysm, due to increased GSK-3b-mediated activation of ROCK and induction of a hypercontractile phenotype.

    • Silvia Villahoz
    • , Paula Sofía Yunes-Leites
    •  & Miguel R. Campanero

  • Article
    | Open Access

    Gluten-free diets are increasingly common in the general population. Here, the authors report the results of a randomised cross-over trial involving middle-aged, healthy Danish adults, showing evidence that a low-gluten diet leads to gut microbiome changes, possibly due to variations in dietary fibres.

    • Lea B. S. Hansen
    • , Henrik M. Roager
    •  & Oluf Pedersen

  • Article
    | Open Access

    Uptake and release of glycerol from the small intestine and adipocytes is facilitated by a subclass of aquaporins (AQP), but how glycerol flow is regulated remains poorly understood. Here authors solve the crystal structure of AQP10 and show how lipolysis is coupled to AQP10 regulation in

    • Kamil Gotfryd
    • , Andreia Filipa Mósca
    •  & Pontus Gourdon

  • Article
    | Open Access

    Excess caloric intake leads to increased thermogenesis in brown adipose tissue, to limit weight gain. Here, the authors show that neuropeptide FF receptor-2 signalling promotes thermogenesis via control of NPY expression in the arcuate nucleus, and that it absence in mice leads to a failure of activation of diet-induced thermogenesis and the development of exacerbated obesity.

    • Lei Zhang
    • , Chi Kin Ip
    •  & Herbert Herzog

  • Article
    | Open Access

    Gut microbiota impact host metabolism and gut microbiome composition reflects dietary habits. Here the authors show that, in animals fed obesogenic diets, changes in gut microbiota precede changes in glucose homeostasis. Importantly, long term exposure of the host to the changed microbiota is required to impair glucose homeostasis.

    • Kevin P. Foley
    • , Soumaya Zlitni
    •  & Jonathan D. Schertzer

  • Article
    | Open Access

    Rare genetic variants can contribute to complex traits but this contribution is not well understood. Here, the authors analyse deep whole genome sequencing data across 1457 individuals from an isolated Greek population and find association of rare variant burdens with cardiometabolic traits.

    • Arthur Gilly
    • , Daniel Suveges
    •  & Eleftheria Zeggini

  • Article
    | Open Access

    Organisms could respond to essential resource limitation by increasing metabolic efficiency or resource acquisition ability. Here, the authors experimentally evolve green algae under different resource limitations and show convergent evolution of core metabolism rather than resource specialization.

    • Manu Tamminen
    • , Alexander Betz
    •  & Anita Narwani

  • Article
    | Open Access

    Increased glycolysis and inflammatory responses have been observed in endothelial cells exposed to disturbed flow. However, the role of endothelial glycolysis in atherosclerosis is unclear. Here the authors unveil a protective role for glycolysis by showing that endothelial deletion of Prkaa1 accelerates atherosclerosis in hyperlipidemic mice through a reduction of glycolytic metabolism.

    • Qiuhua Yang
    • , Jiean Xu
    •  & Yuqing Huo

  • Article
    | Open Access

    GABAergic interneurons are known to provide inhibition to allow computational function of neuronal network. Here, Espinoza and colleagues show that connectivity of granule cells and interneurons in the dentate gyrus of mouse hippocampus are consistent with the circuit architecture capable of performing a winners-take-all mechanism.

    • Claudia Espinoza
    • , Segundo Jose Guzman
    •  & Peter Jonas

  • Article
    | Open Access

    Thyroid dysfunction is a common public health problem and associated with cardiovascular co-morbidities. Here, the authors carry out genome-wide meta-analysis for thyroid hormone (TH) levels, hyper- and hypothyroidism and identify SLC17A4 as a TH transporter and AADAT as a TH metabolizing enzyme.

    • Alexander Teumer
    • , Layal Chaker
    •  & Marco Medici

  • Article
    | Open Access

    Direct electrical brain stimulation can induce widespread changes in neural activity, offering a means to modulate network-wide activity and treat disease. Here, the authors show that the low-frequency functional connectivity profile of a stimulation target predicts where induced theta activity occurs.

    • E. A. Solomon
    • , J. E. Kragel
    •  & M. J. Kahana

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