Physiology

  • Article
    | Open Access

    Activation of brown adipose tissue thermogenesis increases energy expenditure and promotes weight loss in mice. Here the authors identify neurotrophic factor neurotrophin 3 (NT-3) as an adipokine that regulates sympathetic nervous system growth and innervation in adipose tissue and increases white adipose beiging.

    • Xin Cui
    • , Jia Jing
    •  & Hang Shi
  • Article
    | Open Access

    Brown adipose tissue (BAT) in infants has been studied for more than a century, however, the knowledge about its physiological features is limited. Here, the authors investigate the link between BAT thermogenesis and the regulation of temperature in human new-borns with non-invasive infrared thermography.

    • Adela Urisarri
    • , Ismael González-García
    •  & Miguel López
  • Article
    | Open Access

    Cytosolic amino acid concentrations are carefully maintained, but how homeostasis occurs is unclear. Here, the authors show that amino acid transporters primarily determine intracellular amino acid levels and develop a model that predicts a perturbation response similar to experimental data.

    • Gregory Gauthier-Coles
    • , Jade Vennitti
    •  & Stefan Bröer
  • Article
    | Open Access

    The wake-active orexin system plays a central role in the dynamic regulation of glucose homeostasis. Here the authors report that inactivation of the orexin receptor type 1 or 2 in serotonergic neurons differentially regulate systemic glucose homeostasis in the context of diet induced obesity.

    • Xing Xiao
    • , Gagik Yeghiazaryan
    •  & A. Christine Hausen
  • Article
    | Open Access

    Streptomyces bacteria have a linear chromosome, with core genes located in the central region and gene clusters for specialized metabolite biosynthesis found in the ‘arms’. Here, Lioy et al. show that such chromosome structure correlates with genetic compartmentalization, and the onset of metabolic differentiation is accompanied by a rearrangement of chromosome architecture.

    • Virginia S. Lioy
    • , Jean-Noël Lorenzi
    •  & Stéphanie Bury-Moné
  • Article
    | Open Access

    Calcitonin receptor-expressing neurons of the nucleus tractus solitarius contribute to long-term control of food intake and body weight. The authors show that a subset of these cells expresses Prlh and that enhancing Prlh-mediated neurotransmission from the NTS dampens hypothalamically-driven hyperphagia and obesity in mice.

    • Wenwen Cheng
    • , Ermelinda Ndoka
    •  & Martin G. Myers Jr
  • Article
    | Open Access

    There are dynamic interactions between immune cells and β cells that lead to β cell destruction in the context of autoimmune diabetes. Here the authors show that TET2, a methylcytosine dioxygenase, can regulate this interaction and deletion of TET2 can prevent the autoimmune destruction of β cells in mice.

    • Jinxiu Rui
    • , Songyan Deng
    •  & Kevan C. Herold
  • Article
    | Open Access

    Proper meiotic chromosome segregation requires mismatch repair genes MLH1 and MLH3, of which variants occur in the human population. Here, the authors use computational predictions and yeast assays to select human MLH1/3 variants for modelling in mice, observing reproductive defects from abnormal levels of crossing over.

    • Priti Singh
    • , Robert Fragoza
    •  & John C. Schimenti
  • Article
    | Open Access

    Osteoporosis and bone fractures affect millions of patients worldwide and are often due to increased bone resorption. Here the authors identify the cytoplasmic protein ELMO1 as an important ‘signaling node’ promoting the bone resorption function of osteoclasts.

    • Sanja Arandjelovic
    • , Justin S. A. Perry
    •  & Kodi S. Ravichandran
  • Article
    | Open Access

    The sperm head-to-tail coupling apparatus ensures sperm head-tail integrity, but mechanistic insights remain limited. Here the authors demonstrate that CENTLEIN links and controls the interaction between SUN5 and PMFBP1, indicating that its impairments might be associated with acephalic spermatozoa syndrome.

    • Ying Zhang
    • , Chao Liu
    •  & Li Yuan
  • Article
    | Open Access

    Hyaluronan is a naturally occurring linear polysaccharide that together with collagens, enzymes, and glycoproteins forms the extracellular matrix. Here the authors show that adipose tissue overproduction of Hyaluronan reduces fat accumulation in mice fed high-fat diet and improves systemic glucose homeostasis.

    • Yi Zhu
    • , Na Li
    •  & Philipp E. Scherer
  • Article
    | Open Access

    Incretin hormones regulate insulin and glucagon secretion in mammals, but similar peptides have not been characterized in invertebrates. Here the authors show that neuropeptide F functions similar to mammalian incretin in fruit flies, responding to sugar and enhancing insulin-like peptide secretion.

    • Yuto Yoshinari
    • , Hina Kosakamoto
    •  & Ryusuke Niwa
  • Article
    | Open Access

    The mechanisms that mediate the effects of weight loss surgeries such as vertical sleeve gastrectomy (VSG) are incompletely understood. Here the authors show that intestinal FGF15 is necessary to improve glucose tolerance and to prevent the loss of muscle and bone mass after VSG, potentially via protection against bile acid toxicity.

    • Nadejda Bozadjieva-Kramer
    • , Jae Hoon Shin
    •  & Randy J. Seeley
  • Article
    | Open Access

    Nicotinic acid adenine dinucleotide phosphate (NAADP) potent Ca2+ mobilizing second messenger which uniquely triggers Ca2+ release from acidic endolysosomal organelles. Here the authors identify Lsm12 as an NAADP receptor essential for NAADP-evoked Ca2+ release from lysosomes via NAADP binding on its Lsm domain.

    • Jiyuan Zhang
    • , Xin Guan
    •  & Jiusheng Yan
  • Article
    | Open Access

    Developing effective treatments for noncompressible hemorrhages remains a challenge. Here the authors engineer alkylated chitosan sponges with highly interconnective microchannels and demonstrate anti-infective activity, as well as higher pro-coagulant, hemostatic and wound healing capacities compared to clinically-used materials in rat and pig liver models.

    • Xinchen Du
    • , Le Wu
    •  & Meifeng Zhu
  • Article
    | Open Access

    Gut microbiota deficient mice demonstrate enhanced glucose clearance, but which tissues are responsible for this improvement are still unclear. Here the authors report that brown adipose tissue contributes to the enhanced glucose clearance in gut microbiota depleted mice and that this response is dissociated from adaptive thermogenesis.

    • Min Li
    • , Li Li
    •  & John R. Speakman
  • Article
    | Open Access

    Visceral adiposity is a risk factor for cognitive decline, but subcutaneous adipose tissue (SAT) is not and may be protective. Here, the authors show that beige adipocytes are indispensable for the neuroprotective effects of SAT. Beige fat knockout mice were more susceptible to the neuroimmune and cognitive effects of obesity, and in normal mice, SAT transplants protected against chronic obesity via beige fat-dependent mechanisms.

    • De-Huang Guo
    • , Masaki Yamamoto
    •  & Alexis M. Stranahan
  • Article
    | Open Access

    Differentiation of hPSCs to cardiomyocytes suffers from high variability. Here the authors report a label-free live cell imaging platform based on autofluorescence imaging to enable the prediction of cardiomyocyte differentiation efficiency from hPSCs.

    • Tongcheng Qian
    • , Tiffany M. Heaster
    •  & Melissa C. Skala
  • Article
    | Open Access

    The cellular identity and function of the pancreatic polypeptide (Ppy)-producing γ-cells are incompletely understood. Here the authors show that these cells are heterogeneous and display adaptive plasticity to engage in insulin production following β-cell injury, but loss of the Ppy gene or γ-cells in mice does not affect weight or glycemia under basal conditions.

    • Marta Perez-Frances
    • , Léon van Gurp
    •  & Pedro L. Herrera
  • Article
    | Open Access

    Whether thyroid hormones affect gene expression via DNA methylation is not well known. Here the authors show that type 2 deiodinase (D2) converts T4 to produce T3, which prevents DNA methylation of discrete areas in the neonatal liver. In the absence of D2, DNA methylation occurs and is associated with reduced chromatin accessibility in promoters and enhancers and affects gene expression.

    • Tatiana L. Fonseca
    • , Tzintzuni Garcia
    •  & Antonio C. Bianco
  • Article
    | Open Access

    Diverse macrophage subsets are found in adipose tissue where they regulate its physiology. Here, the authors used single-cell RNA sequencing to analyse the effect of post-prandial lipids on adipose tissue macrophages and identify Tim4 as a regulator of ABCA1+ macrophage function and post-prandial cholesterol transport.

    • M. S. Magalhaes
    • , P. Smith
    •  & C. Bénézech
  • Article
    | Open Access

    Theory predicts that organisms in varied environments should evolve to be more phenotypically flexible. Evidence combining genetic and physiological variation with thermal acclimation experiments shows that the thermogenic flexibility of wild juncos is greatest in populations where temperatures are most variable.

    • Maria Stager
    • , Nathan R. Senner
    •  & Zachary A. Cheviron
  • Article
    | Open Access

    Acute pancreatitis is a serious inflammatory disease, which is more severe in diabetic mice. Here the authors use mice lacking pancreatic acinar cell insulin receptors to show that this may be because insulin preserves glycolytic energy supply in acinar cell during pancreatitis, which prevents cytotoxic calcium overload and cell death.

    • Jason I. E. Bruce
    • , Rosa Sánchez-Alvarez
    •  & John A. Williams
  • Article
    | Open Access

    Different types of mesenchymal progenitors participate in ectopic bone formation. Here, the authors show Col2+ lineage cells adopt a lymphatic endothelium cell fate, which regulates local inflammatory microenvironment after trauma, thus influencing heterotopic ossification (HO) development via a FGFR3-BMPR1a pathway.

    • Dali Zhang
    • , Junlan Huang
    •  & Yangli Xie
  • Article
    | Open Access

    Memory T cells are particularly reliant on fatty acid oxidation as a source of energy. Here the authors show this reliance is controlled by AMPK sensing of glucose deprivation that triggers SENP1-Sirt3 signalling, driving fatty acid oxidation and memory differentiation in T cells via deacetylation of YME1L1 to induce mitochondrial fusion.

    • Jianli He
    • , Xun Shangguan
    •  & Jinke Cheng
  • Article
    | Open Access

    Self-powered implantable devices have the potential to extend device operation, though current energy harvesters are both insufficient and inconvenient. Here the authors report on a commercial coin battery-sized high-performance inertia-driven triboelectric nanogenerator based on body motion and gravity that can be used to charge a lithium-ion battery and integrated into a cardiac pacemaker.

    • Hanjun Ryu
    • , Hyun-moon Park
    •  & Sang-Woo Kim
  • Article
    | Open Access

    Reactive oxygen species are required for the long lifespan, and glutathione is an antioxidant. Here the authors show that limiting the consumption of dietary thiols, including those naturally derived from the microbiota, increases proteotoxic stress resistance in worms and human cells, and extends C. elegans lifespan.

    • Ivan Gusarov
    • , Ilya Shamovsky
    •  & Evgeny Nudler
  • Article
    | Open Access

    Neurofibromatosis type 1 (NF1) is a genetic disorder caused by mutations in neurofibromin and associated with disruptions in physiology and behavior. Here the authors show that neurofibromin regulates metabolic homeostasis via a discrete brain circuit in a Drosophila model of NF1.

    • Valentina Botero
    • , Bethany A. Stanhope
    •  & Seth M. Tomchik
  • Article
    | Open Access

    Lactate levels in blood change during hypoxia or exercise, however whether this variable is sensed to evoke adaptive responses is unknown. Here the authors show that oxygen-sensing carotid body cells stimulated by hypoxia are also activated by lactate to potentiate a compensatory ventilatory response.

    • Hortensia Torres-Torrelo
    • , Patricia Ortega-Sáenz
    •  & José López-Barneo
  • Article
    | Open Access

    Osteoarthritis is caused by an imbalance between extracellular matrix synthesis and degradation. Here, the authors show that both strands of microRNA-455, -5p and -3p, target HIF2α and regulate cartilage homeostasis, and show that overexpression of these miRNAs is protective against osteoarthritis in mice.

    • Yoshiaki Ito
    • , Tokio Matsuzaki
    •  & Hiroshi Asahara
  • Article
    | Open Access

    Limited understanding of the interactions between nanoparticle drug carriers and the blood-brain barrier underlies many translational failures in treatments of brain disorders. Here the authors use two-photon microscopy in mice to characterize the receptor-mediated transcytosis of nanoparticles at all steps of delivery from the blood to the brain in vivo.

    • Krzysztof Kucharz
    • , Kasper Kristensen
    •  & Martin Johannes Lauritzen
  • Article
    | Open Access

    Iron is essential during pregnancy for embryo and placental development and maternal health. However, in this study using mouse models, the authors demonstrate that excess maternal iron causes adverse embryo outcomes in pregnancies with underlying systemic inflammation.

    • Allison L. Fisher
    • , Veena Sangkhae
    •  & Elizabeta Nemeth
  • Article
    | Open Access

    Whether the adult testis harbours a somatic progenitor population is unknown. Here, the authors provide evidence that the testis interstitial cells expressing the transcription factor Tcf21 maintain adult testis homeostasis during aging, and act as potential reserve somatic progenitors following injury.

    • Yu-chi Shen
    • , Adrienne Niederriter Shami
    •  & Saher Sue Hammoud
  • Article
    | Open Access

    The human voltage-gated proton channel (hHv1) maintains intracellular pH and membrane potential in sperm and neutrophils. Here, the authors show that albumin activates hHv1, by binding to the channel voltage sensor domains to enhance open probability and increases proton current, and that activation is required to trigger sperm to allow oocyte fertilization and to sustain production and release of immune inflammatory mediators during the neutrophil respiratory burst.

    • Ruiming Zhao
    • , Hui Dai
    •  & Steve A. N. Goldstein
  • Article
    | Open Access

    Bacterial microcompartments (BMCs) are organelles consisting of a protein shell in which certain metabolic reactions take place separated from the cytoplasm. Here, Sutter et al. present a comprehensive catalog of BMC loci, substantially expanding the number of known BMCs and describing distinct types and compartmentalized reactions.

    • Markus Sutter
    • , Matthew R. Melnicki
    •  & Cheryl A. Kerfeld