Metabolic diseases articles within Nature Communications

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  • Review Article
    | Open Access

    The gastrointestinal tract participates in maintaining metabolic homeostasis in part through nutrient-sensing and subsequent gut-brain signalling. Here the authors review the role of small intestinal nutrient-sensing in regulation of energy intake and systemic glucose metabolism, and link high-fat diet, obesity and diabetes with perturbations in these pathways.

    • Frank A. Duca
    • , T. M. Zaved Waise
    •  & Tony K. T. Lam

  • Article
    | Open Access

    Beta cell subpopulations with low expression in PDX1, MAFA, and insulin might contribute to islet function and insulin release. Here the authors show that altering the proportion of PDX1LOW MAFALOW to PDX1HIGH MAFAHIGH cells impairs islet function.

    • Daniela Nasteska
    • , Nicholas H. F. Fine
    •  & David J. Hodson

  • Article
    | Open Access

    GLP-1 is a gastrointestinal peptide that regulates gastric acid secretion and emptying, and due to the rapid degradation of intestinally secreted GLP-1 local gastric production has been suggested. Here the authors report the presence of GLP-1 expressing cells in the rat and human stomach, which contribute to the circulating GLP-1 levels and are affected by weight loss surgeries.

    • Lara Ribeiro-Parenti
    • , Anne-Charlotte Jarry
    •  & André Bado

  • Article
    | Open Access

    The genetic determinants of sex-specific differences in obesity are still incompletely understood. Here, the authors demonstrate that adipocyte specific loss of Trim28 in committed adipocytes leads to sex specific differences in the development of obesity, and that this phenotype is associated with altered metabolic flexibility and lipid metabolism.

    • Simon T. Bond
    • , Emily J. King
    •  & Brian G. Drew

  • 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

    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

    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

    Defective rhythmic metabolism is associated with high-fat diet feeding and obesity. The authors show that the clock gene BMAL1 drives paraventricular hypothalamic neuron activity via rhythmic GABAergic neurotransmission, and that this mediates diurnal metabolism and diet-induced obesity.

    • Eun Ran Kim
    • , Yuanzhong Xu
    •  & Qingchun Tong

  • Article
    | Open Access

    Immune cells are important regulators of adipose tissue function, including adaptive thermogenesis. Here the authors show that mice with Krüppel-like factor 3 (KLF3) deficiency in bone marrow-derived cells have increased adipose tissue beiging which may at least in part be due to altered eosinophil paracrine signaling.

    • Alexander J. Knights
    • , Emily J. Vohralik
    •  & Kate G. R. Quinlan

  • Article
    | Open Access

    White adipose inflammation can occur in obesity and is at least in part mediated by inflammatory immune cells. Here the authors show that the Type I Interferon/Interferon alpha-beta receptor axis promotes an inflammatory, glycolysis associated adipocyte phenotype.

    • Calvin C. Chan
    • , Michelle S. M. A. Damen
    •  & Senad Divanovic

  • Article
    | Open Access

    Overnutrition is associated with hypothalamic ER stress and impaired leptin signaling. Here the authors show that ER stress already occurs in neonates and that treatment with the ER stress relieving drug TUDCA early in life has beneficial metabolic and neurodevelopmental effects.

    • Soyoung Park
    • , Aleek Aintablian
    •  & Sebastien G. Bouret

  • Article
    | Open Access

    Leptin regulates the sympathetic nervous system, energy expenditure and body weight through incompletely understood mechanisms. Here the authors report that Sh2b1 in leptin receptor positive neurons mediates the ability of leptin to stimulate sympathetic nerve activity in brown adipose tissue, body temperature and cold tolerance.

    • Lin Jiang
    • , Haoran Su
    •  & Liangyou Rui

  • Article
    | Open Access

    Genetic variants in the FAM13A locus have been associated with anthropometric and glycemic traits. Here, using fine-mapping, in vitro knockdown studies in pre-adipocytes and in vivo knockout in mice, the authors show that FAM13A is involved in regulating fat distribution and metabolic traits.

    • Mohsen Fathzadeh
    • , Jiehan Li
    •  & Joshua W. Knowles

  • Article
    | Open Access

    Serotonin inhibits adipose tissue thermogenesis. Here the authors show that obese mice housed in thermoneutrality have increased mast cell serotonin synthesis, and that inhibiting this pathway through deletion of mast cell Tph1 increases white adipose tissue browning and protects against diet-induced obesity, insulin resistance and liver steatosis.

    • Julian M. Yabut
    • , Eric M. Desjardins
    •  & Gregory R. Steinberg

  • Article
    | Open Access

    It’s well known that hippocampal synaptic plasticity and memory are impaired in experimental models of metabolic diseases, however, it is unclear if maternal diet or metabolic alterations around the gestational age may multigenerationally affect learning and memory. In this study, authors demonstrate that maternal high fat diet-dependent insulin resistance affects synaptic plasticity and memory of descendants until the third generation via reduced exon specific brain-derived neurotrophic factor expression in the hippocampus of descendants

    • Salvatore Fusco
    • , Matteo Spinelli
    •  & Claudio Grassi

  • Article
    | Open Access

    Nicotinamide adenine dinucleotide (NAD+) sustains cellular energy metabolism, functions as a substrate of Sirt and PARP enzymes, and its supplementation is explored therapeutically in aging and other contexts. Here the authors provide insight into the role of endogenous NAD+ metabolism by studying nicotinamide riboside kinase 1 (NRK1) deficient mice.

    • Audrey Sambeat
    • , Joanna Ratajczak
    •  & Carles Canto

  • Article
    | Open Access

    Nicotine reduces food intake and increases energy expenditure in brown adipose tissue. Here the authors show that nicotine also induces white adipose tissue browning via central kappa opioid receptor action.

    • Patricia Seoane-Collazo
    • , Laura Liñares-Pose
    •  & Miguel López

  • Article
    | Open Access

    IL-36α,β and ɣ are IL-1-related cytokines promoting inflammation in the skin and intestine. Here the authors show they are elevated in individuals with obesity, and that mice lacking the IL-36 receptor antagonist are more resistant to diet-induced obesity and metabolic dysfunction, which depends on intestinal microbiota.

    • Eirini Giannoudaki
    • , Yasmina E. Hernandez-Santana
    •  & Patrick T. Walsh

  • Article
    | Open Access

    Pancreatic islets are composed of alpha-, beta-, as well as delta-cells and appropriate regulation of glucose homeostasis relies on auto- and paracrine cellular communication. Here, the authors study the role of delta-cell filopodia in this context by employing optogenetic and calcium imaging approaches.

    • Rafael Arrojo e Drigo
    • , Stefan Jacob
    •  & Per-Olof Berggren

  • Article
    | Open Access

    Insulin replacement is a valuable therapy for insulin deficiency, however, other therapies are being investigated to restore metabolic homeostasis. Here, the authors identify S100A9 as a leptin induced circulating cue that improves glucose and lipid homeostasis and extends survival in insulin deficient mice.

    • Giorgio Ramadori
    • , Sanda Ljubicic
    •  & Roberto Coppari

  • Article
    | Open Access

    Diabetes is associated with decreased PI3K activation in skeletal muscle. Here, the authors show that p110a is the predominant PI3K subunit in muscle, and show that its ablation in muscle, but not ablation of p110beta, leads to insulin resistance, increased proteosomal and autophagic activity, and altered mitochondria homeostasis in mice.

    • Mengyao Ella Li
    • , Hans P. M. M. Lauritzen
    •  & C. Ronald Kahn

  • Article
    | Open Access

    The mechanisms by which organisms adapt their growth according to the availability of oxygen are incompletely understood. Here the authors identify the Drosophila fat body as a tissue regulating growth in response to oxygen sensing via a mechanism involving Hph inhibition, HIF1-a activation and insulin secretion.

    • Michael J. Texada
    • , Anne F. Jørgensen
    •  & Kim F. Rewitz

  • Article
    | Open Access

    Fasting is known for its beneficial effects on obesity and diabetes-related health complications. Here Zhang et al. show that fasting induces expression of arginase-2 (Arg2) in the liver, and that hepatic Arg2, by suppressing the expression of the regulator of G-protein signalling 16, recapitulates the positive effects of fasting in obesity and diabetes.

    • Yiming Zhang
    • , Cassandra B. Higgins
    •  & Brian J. DeBosch

  • Article
    | Open Access

    Chemically modified mRNA is a new approach for therapeutic protein expression that could be applied to angiogenesis. Here the authors show in a phase 1 clinical trial that a modified mRNA encoding VEGF-A is well tolerated in patients with type 2 diabetes.

    • Li-Ming Gan
    • , Maria Lagerström-Fermér
    •  & Regina Fritsche-Danielson

  • 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

    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

    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

    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

    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

    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

    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

  • 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

    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

    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

    Obesity can affect bone marrow cell differentiation and the generation of myeloid and lymphoid cells. Here, the authors show that diet and obesity, as well as low-dose lipopolysaccharide, can alter Toll-like receptor 4 signaling bone marrow cells to skew the myeloid-lymphoid homeostasis in mice.

    • Ailing Liu
    • , Minhui Chen
    •  & Lisa Borghesi

  • Article
    | Open Access

    Glucagon secretion is promoted during hypoglycemia and inhibited by increased glucose levels. Here, Basco et al. show that glucokinase suppresses glucose-regulated glucagon secretion by modulating the intracellular ATP/ADP ratio and the closure of KATP channels in α-cells.

    • Davide Basco
    • , Quan Zhang
    •  & Bernard Thorens

  • Article
    | Open Access

    White adipose tissue can undergo a process of beiging and acquire functional characteristics similar to brown adipose tissue, including the ability to dissipate energy via uncoupled respiration. Here, Velazquez-Villegas et al. show that activation of the bile acid membrane receptor, TGR5, leads to white adipocyte beiging by promoting mitochondrial fission.

    • Laura A. Velazquez-Villegas
    • , Alessia Perino
    •  & Kristina Schoonjans

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