Endocrine system and metabolic diseases articles within Nature Communications

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  • 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

    Western diet is one of the major causes underlying diabetes, and the microbes residing in the gut playing a critical role in mediating the effects of diet. Here the authors utilize network analysis to discover two species of Lactobacilli decreased by western diet, which improve glucose metabolism and restore of hepatic mitochondria in mice.

    • Richard R. Rodrigues
    • , Manoj Gurung
    •  & Natalia Shulzhenko

  • 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

    Inflammation contributes to the development of metabolic disease through incompletely understood mechanisms. Here the authors report that deletion of the transcription factor KLF2 in myeloid cells leads to increased feeding and weight gain in mice with concomitant peripheral and central tissue inflammation, while overexpression protects against diet-induced metabolic disease.

    • David R. Sweet
    • , Neelakantan T. Vasudevan
    •  & Mukesh K. Jain

  • 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

    Insulinomas are rare, benign beta cell tumours which overproduce insulin and have been associated to epigenetic alterations. Here the authors characterise insulinoma methylomes, finding changes in promoter methylation and chromatin structure proposed to drive the pathological expression of insulin.

    • Esra Karakose
    • , Huan Wang
    •  & Luca Lambertini

  • 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

    Mechanistic inference following GWAS is hampered by the lack of tissue-specific transcriptomic resources. Here the authors combine genetic variants predisposing to type 2 diabetes with human pancreatic islet RNA-seq data. They identify 7741 islet expression quantitative trait loci (eQTLs), providing a resource for functional interpretation of association signals mapping to non-coding sequence.

    • Ana Viñuela
    • , Arushi Varshney
    •  & Mark I. McCarthy

  • Article
    | Open Access

    Inflammasome activation may contribute to type 2 diabetes, but whether targeting inflammasome is beneficial is unclear. Here the authors show that repurposing nucleoside reverse transcriptase inhibitors for inhibiting inflammasome activation is associated with reduced diabetes development in people and improves insulin sensitivity in experimental settings.

    • Jayakrishna Ambati
    • , Joseph Magagnoli
    •  & Bradley D. Gelfand

  • Article
    | Open Access

    Group 2 innate lymphoid cells (ILC2s) are immune cells present in adipose tissue that contribute to metabolic homeostasis. Here the authors show that Death Receptor 3 (DR3) engagement on ILC2s ameliorates glucose tolerance, protects against insulin-resistance onset and reverses established insulin-resistance.

    • Pedram Shafiei-Jahani
    • , Benjamin P. Hurrell
    •  & Omid Akbari

  • 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

    Autophagic activity declines with age in several tissues and is linked to aging-associated functional decline and pathologies. Here the authors show that Rubicon, a negative regulator of autophagy, decreases in adipocytes with age, and its loss leads to adipocyte dysfunction via excess autophagic degradation of SRC-1 and TIF2.

    • Tadashi Yamamuro
    • , Tsuyoshi Kawabata
    •  & Tamotsu Yoshimori

  • Article
    | Open Access

    Vascular endothelial cell (EC) dysfunction contributes to the occurrence of diabetic complications. Here the authors report that in diabetic conditions, upregulation of the RNA binding protein QKI-7 in ECs due to the imbalance of RNA splicing factors CUG-BP and hnRNPM contributes to EC dysfunction, and that in vivo QKI-7 silencing improves blood flow recovery in diabetic mice with limb ischemia.

    • Chunbo Yang
    • , Magdalini Eleftheriadou
    •  & Andriana Margariti

  • 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

  • Article
    | Open Access

    Obesity and type 2 diabetes (T2D) are metabolic disorders characterized by insulin resistance in skeletal muscle. Here, the authors map skeletal muscle enhancer elements dynamically regulated after exposure to free fatty acid palmitate or inflammatory cytokine TNFα and identify target genes involved in metabolic dysfunction in skeletal muscle.

    • Kristine Williams
    • , Lars R. Ingerslev
    •  & Romain Barrès

  • Article
    | Open Access

    The cytokine IFNα is expressed in the islets of individuals with type 1 diabetes and contributes to local inflammation and destruction of beta cells. Here, the authors provide a global multiomics view of IFNα-induced changes in human beta cells at the level of chromatin, mRNA and protein expression.

    • Maikel L. Colli
    • , Mireia Ramos-Rodríguez
    •  & Décio L. Eizirik

  • Article
    | Open Access

    During the progression of type 2 diabetes, insulin-producing β-cells can lose their identity and become reprogrammed into other cell types. Here the authors show that murine diabetic β-cells require the protein Raptor for maintaining β-cell health and preventing them from turning into α-cells, independent of Raptor’s involvement in regulating blood sugar levels.

    • Qinglei Yin
    • , Qicheng Ni
    •  & Guang Ning

  • Article
    | Open Access

    The genetic basis of prolactinomas remains poorly understood. Here, the authors find a recurrent hotspot somatic mutation in the splicing factor 3 subunit B1 (SF3B1R625H) in prolactinomas, and show that this mutation causes aberrant splicing of ESRRG mRNA leading to up-regulation of prolactin.

    • Chuzhong Li
    • , Weiyan Xie
    •  & Yazhuo Zhang

  • Article
    | Open Access

    Beta-adrenergic stimulation of brown adipose tissue leads to thermogenesis via the activating transcription factor 2 (ATF2) mediated expression of the thermogenic genes Ucp1 and Pgc-1α. Here, the authors show that the scaffold protein p62 regulates brown adipose tissue function through modifying ATF2 genomic binding and subsequent Ucp1 and Pgc-1α induction.

    • Katrin Fischer
    • , Anna Fenzl
    •  & Timo D. Müller

  • Article
    | Open Access

    Brown adipose tissue, known produce heat by metabolizing fat, is also secretes molecules capable of communicating with other organs. Here the authors show that brown adipose tissue secretes kininogen, a component of heat system regulation, that provides auto-regulatory inhibitory signaling in brown adipose tissue.

    • Marion Peyrou
    • , Rubén Cereijo
    •  & Francesc Villarroya

  • Article
    | Open Access

    SGLT2 inhibitors, a class of type 2 diabetes medication, reduce cardiovascular events in patients beyond expectation from blood sugar control. Here the authors report a randomized controlled trial showing that SGLT2 inhibitors reduce inflammasome activation in peripheral macrophages, which may contribute to the cardiovascular protection.

    • So Ra Kim
    • , Sang-Guk Lee
    •  & Yong-ho Lee

  • Article
    | Open Access

    Hepatokines are proteins secreted by the liver that can regulate whole body metabolism. Here the authors identify apolipoprotein J as a hepatokine that regulates muscle glucose metabolism and insulin resistance through a low-density lipoprotein receptor-related protein−2 mediated mechanism in mice.

    • Ji A Seo
    • , Min-Cheol Kang
    •  & Young-Bum Kim

  • Article
    | Open Access

    Hepatic steatosis is associated with poor cardiometabolic health, with de novo lipogenesis (DNL) contributing to hepatic steatosis and subsequent insulin resistance. Here, the authors use 1H-MRS methodology to show hepatic SFA fraction is a measure of DNL and specifically may hamper hepatic insulin sensitivity.

    • Kay H. M. Roumans
    • , Lucas Lindeboom
    •  & Vera B. Schrauwen-Hinderling

  • Article
    | Open Access

    Glucagon is elevated Type-2 diabetes, which contributes to poor glucose control in patients with the disease. Here the authors report that secretion of the hormone is controlled by paracrine inhibition, and that resistance of α-cells to somatostatin can explain hyperglucagonemia in type-2 diabetes.

    • Muhmmad Omar-Hmeadi
    • , Per-Eric Lund
    •  & Sebastian Barg

  • Article
    | Open Access

    Brain insulin action regulates eating behavior and whole-body energy fluxes, however the impact of brain insulin resistance on long-term weight and body fat composition is unknown. Here, the authors show that high brain insulin sensitivity is linked to weight loss during lifestyle intervention and associates with a favorable body fat distribution.

    • Stephanie Kullmann
    • , Vera Valenta
    •  & Martin Heni

  • Article
    | Open Access

    Obesity predisposes to type 2 diabetes, but the mechanisms of obesity-associated β cell dysfunction are incompletely understood. Here the authors report that obesity increases the levels of miR-802, which impairs insulin transcription and secretion by targeting NeuroD1 and Fzd5.

    • Fangfang Zhang
    • , Dongshen Ma
    •  & Liang Jin

  • Article
    | Open Access

    Understanding the regulatory mechanisms governing brown and beige adipose mediated thermogenesis is of interest in order to develop therapeutic strategies to treat obesity. Here, the authors show that adipocyte-expressed apoptosis signal-regulating kinase 1 (ASK1) inhibits browning in response to cold, β3 receptor activation, and LPS.

    • Fabrizio C. Lucchini
    • , Stephan Wueest
    •  & Daniel Konrad

  • Article
    | Open Access

    How hormonal signaling in the mammary epithelium controls the surrounding extracellular matrix is unclear. Here, the authors show that a secreted protease, Adamts18, induced by upstream estrogen-progesterone activated Wnt4 in myoepithelial cells, remodels the basement membrane and contributes to mammary epithelial stemness.

    • Dalya Ataca
    • , Patrick Aouad
    •  & Cathrin Brisken

  • 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

    hPSCs in culture acquire a more naïve pluripotent state upon tankyrase inhibition. Here, the authors show that tankyrase inhibitor-regulated naïve hiPSCs from diabetic donors generate more vascular progenitors and more efficient engraftment into mouse retina than conventional PSCs.

    • Tea Soon Park
    • , Ludovic Zimmerlin
    •  & Elias T. Zambidis

  • Article
    | Open Access

    Parabens are preservatives widely used in consumer products including cosmetics and food. Here the authors demonstrate that maternal paraben exposure may contribute to childhood overweight development by an altered neuronal appetite regulation.

    • Beate Leppert
    • , Sandra Strunz
    •  & Tobias Polte

  • Article
    | Open Access

    In response to insulin, liver cells increase de novo lipogenesis via the transcription factors USF-1 and SREBP. Here the authors show that USF-1 recruits JMJD1C, after its phosphorylation by mTOR, to lipogenic promoters where JMJD1C demethylates histone H3, contributing to lipogenesis by an epigenetic mechanism.

    • Jose A. Viscarra
    • , Yuhui Wang
    •  & Hei Sook Sul

  • Article
    | Open Access

    Despite widespread transcription of LncRNA in mammalian systems, their contribution to metabolic homeostasis at the cellular and tissue level remains elusive. Here Pradas-Juni et al. describe a transcription factor–LncRNA pathway that couples hepatocyte nutrient sensing to regulation of glucose metabolism in mice.

    • Marta Pradas-Juni
    • , Nils R. Hansmeier
    •  & Jan-Wilhelm Kornfeld

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