Endocrinology articles within Nature Communications

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  • Article
    | Open Access

    The mechanistic target of rapamycin complex 1 (mTORC1) integrates nutrient and hormonal signals to control metabolism. Here the authors investigate the effects of constitutive nutrient signaling through genetic activation of RagA in adult mice and show that constitutive nutrient signaling regulates the response to feeding-fasting cycles and does not drive liver cancer.

    • Celia de la Calle Arregui
    • , Ana Belén Plata-Gómez
    •  & Alejo Efeyan

  • Article
    | Open Access

    New-onset hyperglycemia and complications of preexisting diabetes have been observed in COVID-19 patients, however, the underlying mechanisms are not fully understood. Here, the authors show that SARS-CoV-2 is detectable in both endocrine and exocrine cells of the pancreata of patients with COVID-19.

    • Charlotte Steenblock
    • , Stefanie Richter
    •  & Stefan R. Bornstein

  • Article
    | Open Access

    Genetic variants in CD36 have been associated with metabolic syndrome. Here, the authors found that lymphatic vessel integrity and lipid transport are influenced by CD36 expression, and lymphatic endothelial cell CD36 deficiency causes visceral obesity and insulin resistance, which are risk factors for metabolic syndrome and diabetes.

    • Vincenza Cifarelli
    • , Sila Appak-Baskoy
    •  & Nada A. Abumrad

  • Article
    | Open Access

    Human pluripotent stem cell (hPSC) derived pancreatic beta cells are a promising and potentially limitless source for cell replacement therapy. Here the authors perform stage-wise chemical screening to develop an improved protocol for hPSC differentiation to functional pancreatic beta cells at high efficiency.

    • Haisong Liu
    • , Ronghui Li
    •  & Juan Carlos Izpisua Belmonte

  • Article
    | Open Access

    Hepatic gluconeogenesis is important for glucose homeostasis and a therapeutic target for type 2 diabetes. Here, the authors show that the RNA-binding adaptor protein Sam68 promotes the expression level of gluconeogenic genes and increases blood glucose levels by stabilizing the transcriptional coactivator CRTC2, while hepatic Sam68 deletion alleviates hyperglycemia in mice.

    • Aijun Qiao
    • , Junlan Zhou
    •  & Gangjian Qin

  • Article
    | Open Access

    Impaired wound healing is a serious complication in diabetic patients, and is associated with reduced HIF1α stability. Here, the authors design a small molecule that stabilizes HIF1α by blocking its interaction with VHL and show that it promotes wound healing in mouse models of diabetes.

    • Guodong Li
    • , Chung-Nga Ko
    •  & Chung-Hang Leung

  • Article
    | Open Access

    Regeneration of insulin-producing beta-cells may become a future alternative treatment of diabetes. Here the authors report a genetic screen in a zebrafish model that mimics the loss of beta-cells in diabetes, and identified that the folate receptor Folr1 or folinic acid treatment can stimulate beta-cell regeneration.

    • Christos Karampelias
    • , Habib Rezanejad
    •  & Olov Andersson

  • Article
    | Open Access

    LncRNAs are implicated in the pathogenesis of a number of diseases. Here, the authors show that the lncRNA Nron suppresses bone resorption, and show that delivery of a functional motif of Nron increases bone mass in mouse models of osteoporosis.

    • Fujun Jin
    • , Junhui Li
    •  & Xiaogang Wang

  • Article
    | Open Access

    As the leading cause of vision loss in working-age adults, diabetic retinopathy requires routinely retinal screening. Here the authors develop a deep learning system that can facilitate the screening by providing real-time image quality assessment, lesions detection, and grades across the disease spectrum.

    • Ling Dai
    • , Liang Wu
    •  & Weiping Jia

  • Article
    | Open Access

    Heterozygous HNF1A mutations can give rise to maturity onset diabetes of the young 3 (MODY3), characterized by insulin secretion defects. Here the authors show that MODY3-related HNF1A mutation in patient hiPSCderived pancreatic cells decreases glucose transporter GLUT2 expression due to compromised DNA binding.

    • Blaise Su Jun Low
    • , Chang Siang Lim
    •  & Adrian Kee Keong Teo

  • Article
    | Open Access

    The soluble bioactive form of the transmembrane protein fibronectin type III domain containing 4 (sFNDC4) has anti-inflammatory effects and improves insulin sensitivity. Here the authors show that liver derived sFNDC4 signals through adipose tissue GPCR GPR116 to promote insulin-mediated glucose uptake.

    • Anastasia Georgiadi
    • , Valeria Lopez-Salazar
    •  & Stephan Herzig

  • Article
    | Open Access

    Interactions between the immune system and adipose tissue contribute to the regulation of body weight, however, the underlying mechanisms remain incompletely understood. Here the authors dissect the role of two structurally and functionally similar immune mediators, BAFF and APRIL, in modifying diet-induced weight gain and adipocyte lipid handling.

    • Calvin C. Chan
    • , Isaac T. W. Harley
    •  & Senad Divanovic

  • Article
    | Open Access

    The pituitary gland plays important roles in the regulation of key physiological functions. Here the authors provide a multiomics atlas including transcriptome, chromatin accessibility, and methylation status of over 70,000 single nuclei (sn) from mouse pituitaries.

    • Frederique Ruf-Zamojski
    • , Zidong Zhang
    •  & Stuart C. Sealfon

  • Article
    | Open Access

    There are few treatments for male infertility. Here, the authors show that the receptor activator of NF-κB ligand (RANKL) signalling pathway has important functions in sperm production and maturation, improves fertility in male mice and shows potential as a male infertility target.

    • Martin Blomberg Jensen
    • , Christine Hjorth Andreassen
    •  & Anders Juul

  • Article
    | Open Access

    The SARS-CoV-2 receptor ACE2 is involved in the Renin-Angiotensin-Aldosterone System (RAAS). Over-activation of RAAS in swine results in a disease state similar to that of COVID-19 in human patients, suggesting that COVID-19 pathophysiology may be driven, at least in part, by an imbalance of this hormonal system.

    • Susanne Rysz
    • , Jonathan Al-Saadi
    •  & Johan Lundberg

  • Article
    | Open Access

    Mutations in components of the MAP kinase pathway are associated with a group of syndromes known as RASopathies. Here, the authors identify gain-of-function mutations in BRAF in patients with RASopathies and congenital hypopituitarisms.  This article demonstrates a central role for BRAF in the development of the hypothalamo-pituitary axis leading to endocrine deficiencies in patients with RASopathies.

    • Angelica Gualtieri
    • , Nikolina Kyprianou
    •  & Carles Gaston-Massuet

  • 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

    Cold acclimation has been shown to have beneficial metabolic effects, including improved insulin sensitivity in patients with type 2 diabetes. Here the authors show that a mild cold acclimation regiment during which overt shivering was prevented did not result in improved insulin sensitivity in a small group of patients with type 2 diabetes.

    • Carlijn M. E. Remie
    • , Michiel P. B. Moonen
    •  & Patrick Schrauwen

  • Article
    | Open Access

    The early identification of metabolic disorders could improve or prevent overt disease. Here the authors show that the circulating concentration of hyocholic acid (HCA) species is decreased in the context of obesity and diabetes and increased after gastric bypass surgery in humans, and further that serum HCA species are predictive of metabolic outcomes in healthy individuals.

    • Xiaojiao Zheng
    • , Tianlu Chen
    •  & Wei Jia

  • Article
    | Open Access

    Dietary changes can impact the microbial constitution of the gastrointestinal tract and modulate the local immune response. Here, the authors show supplementation using lysates of Methylococcus capsulatus Bath result in changes to the microbiota, modulate Treg populations and metabolic read outs in a dietary control murine model.

    • Benjamin A. H. Jensen
    • , Jacob B. Holm
    •  & Tor E. Lea

  • Article
    | Open Access

    Although polycystic ovary syndrome is the most common cause of female infertility, its etiology remains poorly understood. Here, the authors report a rat model that spontaneously exhibits the clinical heterogeneity of this syndrome and demonstrate that the phenotype is developmentally programmed.

    • Camille Bourgneuf
    • , Danielle Bailbé
    •  & Chrystèle Racine

  • Article
    | Open Access

    Autoimmune Addison’s disease is a rare complex disease, which has not yet been characterized by non-biased genetic studies. Here, the authors perform the first GWAS for the disease, identifying nine loci including two coding variants in the gene Autoimmune Regulator (AIRE).

    • Daniel Eriksson
    • , Ellen Christine Røyrvik
    •  & Eystein Sverre Husebye

  • Article
    | Open Access

    The genetic basis of daytime napping and the directional effect of daytime napping on cardiometabolic health are unknown. Here, the authors perform a genome-wide association study on self-reported daytime napping in the UK Biobank and Mendelian randomization to explore causal associations.

    • Hassan S. Dashti
    • , Iyas Daghlas
    •  & Richa Saxena

  • Article
    | Open Access

    Obesity and its associated metabolic changes, including hyperinsulinemia and aberrant circadian rhythms, increases the risk for a variety of cancers including postmenopausal breast cancer. Here, the authors show that restricting when mice eat, but not what or how much they eat, delays breast cancer initiation and reduces tumor growth in obese mice in addition to improving insulin sensitivity and restoring circadian rhythms.

    • Manasi Das
    • , Lesley G. Ellies
    •  & Nicholas J. G. Webster

  • Article
    | Open Access

    Apelin and AVP have opposing effects water balance in humans and rodents. Here, the authors report that a metabolically stable apelin-17 analog, by acting at the kidney level, reduces AVP-induced antidiuresis and improves hyponatremia in rodents, demonstrating a potential approach for treating water metabolism disorders.

    • Adrien Flahault
    • , Pierre-Emmanuel Girault-Sotias
    •  & Catherine Llorens-Cortes

  • Article
    | Open Access

    Islet amyloid polypeptide (IAPP) deposition is associated with islet cell loss in diabetes. Here the authors show that a small molecule autophagy enhancer reduces IAPP accumulation in vitro, and also improves glucose tolerance in hIAPP+ mice fed high-fat diet, accompanied by reduced hIAPP accumulation, in vivo.

    • Jinyoung Kim
    • , Kihyoun Park
    •  & Myung-Shik Lee

  • Article
    | Open Access

    Sex differences in fasting glucose and insulin have been identified, but the genetic loci underlying these differences have not. Here, the authors perform a meta-analysis of genome-wide association studies to detect sex-specific and sex-dimorphic loci associated with fasting glucose and insulin.

    • Vasiliki Lagou
    • , Reedik Mägi
    •  & Inga Prokopenko

  • 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

    Here, the authors investigate associations of vitamin D metabolites with gut microbiome in a cross-sectional analysis of 567 elderly men enrolled in the Osteoporotic Fractures in Men (MrOS) Study and find larger alpha-diversity correlates with high 1,25(OH)2D and high 24,25(OH)2D and higher ratios of activation and catabolism.

    • Robert L. Thomas
    • , Lingjing Jiang
    •  & Deborah M. Kado

  • 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

    Gut microbial metabolism of nutrients contributes to metabolic diseases, and the histidine metabolite imidazole propionate (ImP) is produced by type 2 diabetes (T2D) associated microbiome. Here the authors report that circulating ImP levels are increased in subjects with prediabetes or T2D in three European populations, and this increase associates with altered gut microbiota rather than dietary histidine.

    • Antonio Molinaro
    • , Pierre Bel Lassen
    •  & Fredrik Bäckhed

  • Article
    | Open Access

    Metformin is an anti-diabetic drug that has shown promise to reduce M. tuberculosis susceptibility. Here the authors show that this effect is a result of metformin-mediated activation of anti-mycobacterial memory-like antigen-inexperienced CD8+CXCR3+ T cells, an effect that also boosts response to BCG vaccination.

    • Julia Böhme
    • , Nuria Martinez
    •  & Amit Singhal

  • Article
    | Open Access

    Lifestyle interventions are first-line treatment for women with polycystic ovary syndrome (PCOS), but the optimal diet remains undefined. Here the authors identify an optimum dietary macronutrient balance that can rectify PCOS reproductive traits in a mouse model of PCOS, while metabolic features were less sensitive to diet changes.

    • Valentina Rodriguez Paris
    • , Samantha M. Solon-Biet
    •  & Kirsty A. Walters

  • 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

    The gut microbiome affects systemic metabolism and is a therapeutic target for type 2 diabetes. Here the authors demonstrate in a randomized controlled trial that effects of berberine, a plant alkaloid known to lower blood glucose, may be explained by the inhibition of Ruminococcus bromii mediated biotransformation of the bile acid deoxycholic acid.

    • Yifei Zhang
    • , Yanyun Gu
    •  & Weiqing Wang

  • Article
    | Open Access

    Both agonism and antagonism of the glucose-dependent insulinotropic polypeptide receptor (GIPR) lead to weight loss in combination with glucagon-like peptide-1 receptor agonists in preclinical models. Here the authors show that this may be explained by desensitization of GIPR activity by chronic GIPR agonism in vitro and in vivo.

    • Elizabeth A. Killion
    • , Michelle Chen
    •  & David J. Lloyd

  • Article
    | Open Access

    Time restricted feeding has several health benefits. Here the authors perform a randomised cross-over study with 11 men with overweight/obesity to investigate how time restricted feeding affects skeletal muscle and serum, and report that it does not affect the core circadian machinery, but modifies periodicity in amino acid related metabolites and transporters.

    • Leonidas S. Lundell
    • , Evelyn B. Parr
    •  & John A. Hawley

  • Article
    | Open Access

    In rodent models of type 2 diabetes, sustained remission of hyperglycemia can be induced by FGF1 action in the mediobasal hypothalamus. Here, the authors show that FGF1-injection is followed by marked changes in glial cell populations and that the sustained glycemic response is dependent on intact melanocortin signaling.

    • Marie A. Bentsen
    • , Dylan M. Rausch
    •  & Tune H. Pers

  • Article
    | Open Access

    Epigenetic regulators contribute to the modulation of adipose thermogenesis by sensing environmental cues and regulating gene expression in response. Here the authors report that a DNA demethylase TET1 mediates epigenetic changes to repress thermogenic genes in mouse adipose tissue.

    • Sneha Damal Villivalam
    • , Dongjoo You
    •  & Sona Kang

  • 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

    DPP4 inhibitors are used for the treatment of diabetes, but the impact of DPP4 activity and soluble DPP4 on development of diabetes-associated inflammation remains uncertain. Here the authors study whether DPP4 inhibition controls sDPP4 and inflammatory biomarkers, and demonstrate that DPP4 inhibition is dissociated from changes in inflammation in mice and humans.

    • Laurie L. Baggio
    • , Elodie M. Varin
    •  & Daniel J. Drucker

  • Article
    | Open Access

    Recently, the first orally-administered ultra-long acting insulin was shown to have clinical efficacy. Here, the authors report the molecular engineering, as well as the biological and pharmacological properties of these insulin analogues.

    • Frantisek Hubálek
    • , Hanne H. F. Refsgaard
    •  & Thomas Kjeldsen

  • Article
    | Open Access

    Inflammation, immune cells and the host microbiota are intimately linked in the pathophysiology of obesity and diabetes. Here the authors show mucosal-associated invariant T cells fuel inflammation in the tissues and serve a function in promoting metabolic breakdown, polarising macrophage populations and inducing dysbiosis of the intestinal microbiota.

    • Amine Toubal
    • , Badr Kiaf
    •  & Agnès Lehuen

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