Metabolism

  • Article
    | Open Access

    Circulating adiponectin controls sensitivity to insulin in tissues. Here, Arquier et al. show that adiponectin receptor activity in neurons of the Drosophila brain controls insulin response in peripheral tissues via juvenile hormone signaling.

    • Nathalie Arquier
    • , Marianne Bjordal
    •  & Pierre Léopold
  • Article
    | Open Access

    While phosphorylation is an essential post-translational modification in eukaryotes only recently the phosphoproteome of prokaryotes has been provided. Here, Schastnaya et al. mutate 52 phosphosites on 23 E. coli enzymes and apply metabolomics to provide evidence for the functional relevance of bacterial phosphorylation events.

    • Evgeniya Schastnaya
    • , Zrinka Raguz Nakic
    •  & Uwe Sauer
  • Article
    | Open Access

    Berberine is a compound with glucose-lowering effects in mice and humans. Here, the authors show that in mice berberine has beneficial glycemic effects by promoting insulin secretion, which requires the potassium channel KCNH6 in beta cells, and that berberine can promote insulin secretion in healthy men in a phase 1 clinical trial.

    • Miao-Miao Zhao
    • , Jing Lu
    •  & Jin-Kui Yang
  • 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

    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

    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

    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

    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

    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

    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
  • Article
    | Open Access

    Abnormal folate metabolism in mice results in transgenerational epigenetic inheritance of congenital malformations. Here, the authors provide evidence that defective folate metabolism causes germline epigenetic instability and observe multigenerational misexpression of Hira in embryos, implicating Hira transcript levels as a biomarker of maternal phenotypic inheritance.

    • Georgina E. T. Blake
    • , Xiaohui Zhao
    •  & Erica D. Watson
  • Article
    | Open Access

    During the expansion of adipose tissue adipocyte progenitor cells proliferate and undergo adipogenesis. Here, the authors show that adipocyte progenitor cell proliferation in visceral adipose tissue has a diurnal pattern, which is dependent on both energy intake and the circadian clock.

    • Aleix Ribas-Latre
    • , Rafael Bravo Santos
    •  & Kristin L. Eckel-Mahan
  • Article
    | Open Access

    Diet-induced changes in the microbiome have been associated with obesity. Here, using a mouse model, the authors show that a mixed protein source found in western diets exacerbates diet-induced obesity and insulin resistance by potentiating hepatic mTORC1/S6K1 signaling via microbial production of branched-chain fatty acids (BCFA).

    • Béatrice S.-Y. Choi
    • , Noëmie Daniel
    •  & André Marette
  • Article
    | Open Access

    During insulin-resistance, the compensatory expansion of beta-cell mass is able to delay or the onset of overt type 2 diabetes. Here, the authors report that beta-arrestin-1, an intracellular protein known to regulate signalling through G protein-coupled receptors, is essential for beta-cell replication and function in insulin-resistant mice.

    • Luiz F. Barella
    • , Mario Rossi
    •  & Jürgen Wess
  • Article
    | Open Access

    The brain is sensitive to oxygen deprivation. Here, the authors show in experimental animals that sensitivity to hypoxia is inversely related to the level of sulfide:quinone oxidoreductast (SQOR) and the capacity to catabolize sulfide in the brain.

    • Eizo Marutani
    • , Masanobu Morita
    •  & Fumito Ichinose
  • Review Article
    | Open Access

    Circadian clocks link physiologic processes to environmental conditions and a mismatch between internal and external rhythms has negative effects on organismal health. In this review, the authors discuss the interactions between circadian clocks and dietary interventions targeted to promote healthy aging.

    • Victoria A. Acosta-Rodríguez
    • , Filipa Rijo-Ferreira
    •  & Joseph S. Takahashi
  • Article
    | Open Access

    The mechanisms driving metabolic dysfunction in obesity remain incompletely understood. Here, the authors show that the levels of Hippo pathway effector YAP are reduced in muscle from individuals with insulin resistance and obese-diabetic mice, and that YAP promotes skeletal muscle lipid metabolism and limits adiposity in obese mice.

    • K. I. Watt
    • , D. C. Henstridge
    •  & P. Gregorevic
  • Review Article
    | Open Access

    At the centre of intestinal health and the fight against obesity and metabolic syndrome is the intestinal microbiota and its interaction with our immune systems. Here the authors Review the current understanding of how these systems interact and how we can capitalize on recent advances to provide better therapeutic options.

    • Saad Khan
    • , Helen Luck
    •  & Daniel A. Winer
  • Article
    | Open Access

    Mediators of insulin signalling are targets of cullin-RING ubiquitin ligases (CRL) that mediate protein degradation, but the role of protein degradation in insulin signalling is incompletely understood. Here, the authors identified a glucose-responsive CRL4-COP1-ETV5 proteolytic axis that promotes insulin secretion, and is inhibited under hypoglycemia.

    • Hong Lin
    • , Yuan Yan
    •  & Feng Rao
  • Article
    | Open Access

    Whether chronic inflammation contributes to metabolic disease through the dysregulation of circadian systems remains incompletely understood in humans. Here the authors show that circadian clock function is perturbed in adipose tissue from individuals with obesity, and that inhibition of NFkB improves clock function.

    • Eleonore Maury
    • , Benoit Navez
    •  & Sonia M. Brichard
  • Article
    | Open Access

    The ventromedial hypothalamus regulates systemic glucose metabolism. Here the authors show that cytosolic phospholipase A2 mediated phospholipid metabolism contributes to this regulation in healthy animals but exert deteriorating effects on glucose homeostasis under high-fat-diet feeding.

    • Ming-Liang Lee
    • , Hirokazu Matsunaga
    •  & Chitoku Toda
  • Article
    | Open Access

    Beige and brown fat may influence systemic metabolism through secreted signals. Here the authors identify a panel of metabolites secreted from beige and brown fat cells, which signal to influence fat tissue and skeletal muscle metabolism and have anti-obesity effects in mouse models of obesity and diabetes.

    • Anna Whitehead
    • , Fynn N. Krause
    •  & Lee D. Roberts
  • Article
    | Open Access

    Type 2 diabetes is associated with chronic inflammation and is characterized by insulin resistance. Here, the authors identify a crucial role for endothelial BMPER function in glucose homeostasis, and BMPER overexpression was shown to alleviate insulin resistance and hyperglycemia in diabetic mice.

    • Hua Mao
    • , Luge Li
    •  & Xinchun Pi
  • Article
    | Open Access

    Dietary restriction (DR) can increase protein persulfidation but the tissue specificity of this process is not well understood. Here, the authors compare organ-specific protein persulfidomes in young and aged mice under DR, and show that DR-dependent persulfidome changes depend on cystathionine γ-lyase.

    • Nazmin Bithi
    • , Christopher Link
    •  & Christopher Hine