Endocrinology

  • Article
    | Open Access

    Gut microbiota alterations, including enrichment of flagellated bacteria, are associated with metabolic syndrome and chronic inflammatory diseases. Here, Tran et al. show, in mice, that elicitation of mucosal anti-flagellin antibodies protects against experimental colitis and ameliorates diet-induced obesity.

    • Hao Q. Tran
    • , Ruth E. Ley
    •  & Benoit Chassaing
  • Article
    | Open Access

    The adipokine leptin modulates intestinal inflammation in mice. Here the authors describe a patient with inflammatory bowel disease and lipodystrophy, providing evidence that leptin aggravates intestinal inflammation with proinflammatory effects on leukocytes that are reversible by TNFα blockade.

    • Jörn F. Ziegler
    • , Chotima Böttcher
    •  & Carl Weidinger
  • Article
    | Open Access

    The invasion of epithelial tumours often depends on the epithelial-mesenchymal transition. Here, the authors report that intracellular activation of thyroid hormone by the D2 deiodinase enzyme promotes invasion and progression of squamous cell carcinoma by transcriptionally up-regulating ZEB-1.

    • Caterina Miro
    • , Emery Di Cicco
    •  & Monica Dentice
  • Article
    | Open Access

    Mutations in the chloride channel ClC-2 have been associated with familial forms of hyperaldosteronism. Here, Schewe et al. generated a mouse model carrying the most common mutation found in patients and find it recapitulates key features of the disease, providing a unique tool for future studies on its pathogenesis.

    • Julia Schewe
    • , Eric Seidel
    •  & Ute Scholl
  • Article
    | Open Access

    Type 1 as well as type 2 diabetes are characterized by a loss of insulin-producing β-cells. Here the authors show that the FDA-approved drug neratinib has beneficial effects on β-cell survival, insulin secretion, and glycemic control in mouse models of diabetes.

    • Amin Ardestani
    • , Sijia Li
    •  & Kathrin Maedler
  • Article
    | Open Access

    Mutations in the chloride channel ClC-2 have been found in primary aldosteronism (PA). Here, Göppner et al. generate transgenic mice expressing a mutant form of ClC-2 that displays increased chloride currents like patient mutations, and find it recapitulates the key pathological features of PA.

    • Corinna Göppner
    • , Ian J. Orozco
    •  & Thomas J. Jentsch
  • Article
    | Open Access

    Surgical weight-loss interventions improve insulin sensitivity via incompletely understood mechanisms. Here the authors assess skeletal muscle epigenetic changes in individuals with obesity following metabolic surgery and compare them with data from individuals without obesity.

    • Sofiya Gancheva
    • , Meriem Ouni
    •  & Michael Roden
  • Article
    | Open Access

    The effect of diet-induced obesity on intestinal B cell populations is not well understood despite emerging evidence of a critical role for the intestinal immune system in contributing to insulin resistance. Here, the authors show important functions of IgA in regulating metabolic disease and for intestinal immunity in modulating systemic glucose metabolism.

    • Helen Luck
    • , Saad Khan
    •  & Daniel A. Winer
  • 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

    The circadian clock regulates rhythms of behavior and physiology and the timing of circadian rhythms in liver is influenced by food intake. Here, the authors identify the hepatokine Angptl8 as a mediator of liver clock food entrainment.

    • Siyu Chen
    • , Mengyang Feng
    •  & Chang Liu
  • Article
    | Open Access

    Type 2 diabetes (T2D) is prevalent in populations worldwide, however, mostly studied in European and mixed-ancestry populations. Here, the authors perform a genome-wide association study for T2D in over 5,000 sub-Saharan Africans and identify a locus, ZRANB3, that is specific for this population.

    • Adebowale A. Adeyemo
    • , Norann A. Zaghloul
    •  & Charles N. Rotimi
  • Article
    | Open Access

    Type 2 diabetes is associated with islet amyloid deposits derived from islet amyloid polypeptide (IAPP) expressed by β-cells. Here the authors show that IAPP misfolded protein stress induces the hypoxia inducible factor 1 alpha injury repair pathway and activates survival metabolic changes mediated by PFKFB3.

    • Chiara Montemurro
    • , Hiroshi Nomoto
    •  & Slavica Tudzarova
  • Article
    | Open Access

    Our understanding of the functional link between differential DNA methylation and type 2 diabetes and obesity remains limited. Here the authors present a blood-based EWAS of fasting glucose and insulin among 4808 non-diabetic Europeans and identify nine CpGs not previously implicated in glucose, insulin homeostasis and diabetes.

    • Jun Liu
    • , Elena Carnero-Montoro
    •  & Cornelia M. van Duijn
  • Article
    | Open Access

    Pancreatic beta-cell glucose metabolism is coupled to insulin secretion. Here the authors set out to characterize changes in beta-cell metabolism in hyperglycemia which may contribute to insufficient insulin secretion in type 2 diabetes and, using a multi-omics approach, find that mitochondrial metabolism is perturbed.

    • Elizabeth Haythorne
    • , Maria Rohm
    •  & Frances M. Ashcroft
  • Article
    | Open Access

    Mitochondrial uncoupling is a treatment strategy for metabolic diseases that reduces the efficiency of mitochondrial oxidative phosphorylation and ATP generation. Here the authors characterize the pharmacokinetic and therapeutic properties of the liver-localized mitochondrial uncoupler OPC-163493, which leads to amelioration of diabetes and hypertension in several rodent disease models.

    • Naohide Kanemoto
    • , Takashi Okamoto
    •  & Seiji Sato
  • Article
    | Open Access

    Neurons expressing pro-opiomelanocortin (Pomc) regulate food intake and body weight. Here the authors show that Steroid Receptor Coactivator-1 (SRC-1) regulates the function of Pomc expressing neurons, and that rare heterozygous variants found in obese individuals lead to loss of SRC-1 function.

    • Yongjie Yang
    • , Agatha A. van der Klaauw
    •  & Yong Xu
  • Article
    | Open Access

    Glucagon-like peptide 1 (GLP-1) is released from intestinal L-cells following nutrient uptake and enhances insulin release as well as promotes satiety. Here, the authors demonstrate that GLP-1 secreting cells release ATP and that this stimulates nodose neurons and enterocytes in a paracrine manner in vitro.

    • Van B. Lu
    • , Juraj Rievaj
    •  & Frank Reimann
  • Article
    | Open Access

    Endoplasmic reticulum (ER) stress has been proposed to play a role in metabolic diseases. Here, Sasako and colleagues identify stromal cell-derived factor 2 like 1 (Sdf2l1) as a regulator of the ER stress response to feeding in the liver, and suggest that its downregulation may promote diabetes and hepatic steatosis in humans.

    • Takayoshi Sasako
    • , Mitsuru Ohsugi
    •  & Kohjiro Ueki
  • Article
    | Open Access

    Reduction in food intake elicits neuroendocrine adaptations to counterregulate the negative energy balance, e.g. via reduction in leptin levels. Here, the authors identify an additional starvation signal, growth hormone (GH). Blocking GH receptor attenuates the fall of whole body energy expenditure during food deprivation in mice.

    • Isadora C. Furigo
    • , Pryscila D. S. Teixeira
    •  & J. Donato Jr
  • Article
    | Open Access

    Insulin-related gene (Insig) negatively regulates hepatic fatty acid synthesis, a process involved in development of non-alcoholic fatty liver disease (NAFLD). Here, the authors show that AMPK activation by metformin promotes Insig phosphorylation, stabilizing it and inhibiting lipogenic gene expression. This is protective against steatosis in diabetic mice.

    • Yamei Han
    • , Zhimin Hu
    •  & Yu Li
  • 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

    Glucocorticoids (GCs) are widely used anti-inflammatory drugs; however, long-term treatment causes metabolic side effects. Here, the authors show that E47 is a modulator of glucocorticoid receptor activity for a subset of target genes in mouse liver, and that loss of E47 protects mice from hyperglycemia and hepatic steatosis in response to GCs.

    • M. Charlotte Hemmer
    • , Michael Wierer
    •  & N. Henriette Uhlenhaut
  • Article
    | Open Access

    Estrogen promotes negative energy balance and preserves skeletal physiology. Here the authors show that loss of estrogen signalling after ablating estrogen receptor alpha (ERa) in specific hypothalamic neuronal populations leads to a marked sex-dependent increase in bone mass in female mice.

    • Candice B. Herber
    • , William C. Krause
    •  & Holly A. Ingraham
  • 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

    Thyroid dysfunction is a common public health problem and associated with cardiovascular co-morbidities. Here, the authors carry out genome-wide meta-analysis for thyroid hormone (TH) levels, hyper- and hypothyroidism and identify SLC17A4 as a TH transporter and AADAT as a TH metabolizing enzyme.

    • Alexander Teumer
    • , Layal Chaker
    •  & Marco Medici
  • Article
    | Open Access

    The onset of mammalian puberty is sensitive to metabolic changes and nutritional status, but the mechanisms underlying this phenomenon are poorly understood. Here the authors show that the epigenetic regulator of transcription, SIRT1, mediates the effects of under and overnutrition on pubertal timing by controlling the expression of Kiss1 in hypothalamic neurons.

    • M. J. Vazquez
    • , C. A. Toro
    •  & M. Tena-Sempere
  • Article
    | Open Access

    Emerging studies suggest that p53 is an important regulator of energy metabolism, yet there is little known about the metabolic function of this tumor suppressor in the hypothalamus. Here, authors illustrate that p53, specifically in AgRP neurons, is required for adaptation to diet-induced obesity.

    • Mar Quiñones
    • , Omar Al-Massadi
    •  & Ruben Nogueiras
  • Article
    | Open Access

    In this study the authors report USP48 and BRAF are frequently mutated in USP8 wild-type corticotroph adenomas, and cause Cushing’s disease mainly through promoting the promoter activity of POMC. Inhibition of BRAF may be a promising therapeutic strategy for the treatment of patients with BRAF-mutated corticotroph adenomas.

    • Jianhua Chen
    • , Xuemin Jian
    •  & Yongyong Shi
  • Article
    | Open Access

    Control of transgene expression should ideally be easy and with minimal side effects. Here the authors present a synthetic biology-based approach in which the caffeine in coffee regulates a genetic circuit controlling glucagon-like peptide 1 expression in diabetic mice.

    • Daniel Bojar
    • , Leo Scheller
    •  & Martin Fussenegger
  • Article
    | Open Access

    Steatosis is characterized by initial accumulation of lipids, followed by inflammation and ultimately fibrosis. Here the authors show that the histone demethylase Plant Homeodomain Finger 2 protects liver form steatosis progression by acting as a co-activator of ChREBP, thus, favouring lipid accumulation without inflammation.

    • Julien Bricambert
    • , Marie-Clotilde Alves-Guerra
    •  & Renaud Dentin
  • Article
    | Open Access

    Testosterone deficiency is associated with autoimmunity and increased B cell numbers, but the underlying mechanism is unclear. Here the authors show that testosterone may modulate the production of B cell survival factor BAFF by fibroblastic reticular cells via regulation of splenic neurotransmitter levels.

    • Anna S. Wilhelmson
    • , Marta Lantero Rodriguez
    •  & Åsa Tivesten
  • 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

    The timing of female reproductive capacity is influenced by genetic and environmental factors. Here, in genome-wide association studies, the authors identify genetic loci for age at menarche and onset of menopause in Japanese women, and highlight differences with European populations.

    • Momoko Horikoshi
    • , Felix R. Day
    •  & John. R. B. Perry
  • Article
    | Open Access

    M1-like polarization of macrophages is thought to control adipose inflammation and associated insulin resistance and metabolic syndrome. Here the authors show that macrophage-specific deletion of the OxPhos-related gene Crif1 results in an M1-like phenotype in mice, and that the effects can be reversed by recombinant GDF15.

    • Saet-Byel Jung
    • , Min Jeong Choi
    •  & Minho Shong
  • Article
    | Open Access

    Sexual dimorphism exists in a number of physiological processes, including energy homeostasis. Here, the authors show that pro-opiomelanocortin neurons in female mice fire more rapidly than males, and that deletion of the transcription TAp63 leads to a reduced neuronal firing rate and a male-like susceptibility to diet-induced obesity.

    • Chunmei Wang
    • , Yanlin He
    •  & Yong Xu