Featured
Article
|Open Access
A comprehensive spatio-cellular map of the human hypothalamusHYPOMAP integrates single-nucleus RNA sequencing and spatial transcriptomic data to create a comprehensive spatio-cellular map of the human hypothalamus.
- John A. Tadross
- ,Lukas Steuernagel
- & Giles S. H. Yeo
Article
|Open Access
NK2R control of energy expenditure and feeding to treat metabolic diseasesIn mouse and nonhuman primate models, treatment with selective, long-acting neurokinin 2 receptor agonists aids weight loss by suppressing appetite and increasing energy expenditure, as well as by increasing insulin sensitivity.
- Frederike Sass
- ,Tao Ma
- & Zachary Gerhart-Hines
Article
|Open Access
Glucose-sensitive insulin with attenuation of hypoglycaemiaNNC2215 is an insulin conjugate that can reversibly adjust its bioactivity in response to a diabetes-relevant glucose range in vivo.
- Thomas Hoeg-Jensen
- ,Thomas Kruse
- & Rita Slaaby
Article |
A brain-to-gut signal controls intestinal fat absorptionNeurons in the dorsal motor nucleus of vagus are involved in the absorption of fat in the intestine, and the natural compound puerarin shows utility in modulating this brain–gut axis to reduce fat absorption.
- Qianqian Lyu
- ,Wenzhi Xue
- & Weiqing Wang
Article
|Open Access
Genetic links between ovarian ageing, cancer risk and de novo mutation ratesAnalyses focusing on protein-truncating variants from 106,973 women from in the UK Biobank identify variants in genes that reinforce the link between reproductive lifespan in women and cancer risk in both sexes.
- Stasa Stankovic
- ,Saleh Shekari
- & Anna Murray
Article |
Control of lipolysis by a population of oxytocinergic sympathetic neuronsOxytocin derived from peripheral sympathetic neurons is shown to regulate lipolysis and systemic metabolism.
- Erwei Li
- ,Luhong Wang
- & Evan D. Rosen
Article |
Quasi-experimental evaluation of a nationwide diabetes prevention programmeAnalysis of the largest behaviour change programme for prediabetes globally provides causal evidence that lifestyle advice and counselling implemented at scale can improve key cardiovascular risk factors.
- Julia M. Lemp
- ,Christian Bommer
- & Pascal Geldsetzer
Article |
Mammary duct luminal epithelium controls adipocyte thermogenic programmeIn mice, sympathetic nerves associated with female mammary glands control the secretion of thermogenesis-controlling factors by epithelial cells in the adipocyte niche, revealing sex-specific differences in adipose thermogenesis.
- Sanil Patel
- ,Njeri Z. R. Sparman
- & Prashant Rajbhandari
Article
|Open Access
GDF15 promotes weight loss by enhancing energy expenditure in muscleGDF15 treatment in mice counteracts compensatory reductions in energy expenditure, resulting in greater weight loss and reductions in non-alcoholic fatty liver disease compared to caloric restriction alone.
- Dongdong Wang
- ,Logan K. Townsend
- & Gregory R. Steinberg
Article
|Open Access
Post-translational control of beige fat biogenesis by PRDM16 stabilizationThe ubiquitin E3 ligase CUL2–APPBP2 determines PRDM16 protein stability by catalysing PRDM16 polyubiquitination in beige fat.
- Qiang Wang
- ,Huixia Li
- & Shingo Kajimura
Article |
Autoantibody mimicry of hormone action at the thyrotropin receptorCryo-electron microscopy structures of the thyrotropin receptor reveal the basis for the activation of the receptor by autoantibodies in patients with Graves’ disease.
- Bryan Faust
- ,Christian B. Billesbølle
- & Aashish Manglik
Article |
Maternal inheritance of glucose intolerance via oocyte TET3 insufficiencyPregestational hyperglycaemia in mothers increases the probability of glucose intolerance in the offspring, an effect controlled by TET3-dependent DNA demethylation of genes involved in insulin secretion.
- Bin Chen
- ,Ya-Rui Du
- & Hefeng Huang
Article |
IL-27 signalling promotes adipocyte thermogenesis and energy expenditureTherapeutic administration of IL-27—serum levels of which are decreased in individuals with obesity—improves thermogenesis, protects against diet-induced obesity and ameliorates insulin resistance in mouse models of obesity.
- Qian Wang
- ,Dehai Li
- & Zhinan Yin
Article |
MC3R links nutritional state to childhood growth and the timing of pubertyMC3R deficiency is associated with a delay in the onset of puberty, and a reduction in growth and lean mass.
- B. Y. H. Lam
- ,A. Williamson
- & S. O’Rahilly
Article |
Genetic insights into biological mechanisms governing human ovarian ageingHundreds of genetic loci associated with age at menopause, combined with experimental evidence in mice, highlight mechanisms of reproductive ageing across the lifespan.
- Katherine S. Ruth
- ,Felix R. Day
- & John R. B. Perry
Article |
Asymmetric activation of the calcium-sensing receptor homodimerCryo-EM structures of human calcium-sensing receptor reveal intrinsic asymmetry in the receptor homodimer upon activation that is stabilized by calcimimetic drugs adopting distinct poses in the two protomers, priming one protomer for G-protein coupling.
- Yang Gao
- ,Michael J. Robertson
- & Georgios Skiniotis
Article |
snRNA-seq reveals a subpopulation of adipocytes that regulates thermogenesisSingle-nucleus RNA sequencing in mouse and human adipose tissue identifies a subpopulation of adipocytes that regulates thermogenesis in neighbouring adipocytes in a paracrine manner by modulating acetate signalling.
- Wenfei Sun
- ,Hua Dong
- & Christian Wolfrum
Article |
A leptin–BDNF pathway regulating sympathetic innervation of adipose tissueThe authors show that leptin signalling regulates the plasticity of sympathetic architecture of adipose tissue via a top-down neural pathway that is crucial for energy homeostasis.
- Putianqi Wang
- ,Ken H. Loh
- & Jeffrey Friedman
Article |
Glucagon stimulates gluconeogenesis by INSP3R1-mediated hepatic lipolysisA role and mechanism of action are identified for INSP3R1 in the stimulation of hepatic gluconeogenesis and mitochondrial oxidation by glucagon, suggesting that INSP3R1 may be a target for ameliorating dysregulation of hepatic glucose metabolism.
- Rachel J. Perry
- ,Dongyan Zhang
- & Gerald I. Shulman
Article |
The structure of human thyroglobulinThe cryo-electron microscopy structure of human thyroglobulin reveals that proximity, flexibility and solvent exposure are key characteristics of its hormonogenic tyrosine pairs, and provides a framework for understanding the formation of thyroid hormones.
- Francesca Coscia
- ,Ajda Taler-Verčič
- & Jan Löwe
Article |
GDF15 mediates the effects of metformin on body weight and energy balanceIn mouse studies, metformin treatment results in increased secretion of growth/differentiation factor 15 (GDF15), which prevents weight gain in response to high-fat diet, and GDF15-independent lowering of circulating blood glucose.
- Anthony P. Coll
- ,Michael Chen
- & Stephen O’Rahilly
Review Article |
The integrative biology of type 2 diabetesA Review of studies into insulin resistance and hepatic gluconeogenesis associated with obesity and type 2 diabetes.
- Michael Roden
- & Gerald I. Shulman
Article |
Diabetes relief in mice by glucose-sensing insulin-secreting human α-cellsIslet non-β-cells from non-diabetic and diabetic human donors are modified via the transcription factors PDX1 and MAFA to produce and secrete insulin in response to glucose.
- Kenichiro Furuyama
- ,Simona Chera
- & Pedro L. Herrera
Letter |
A stromal cell population that inhibits adipogenesis in mammalian fat depotsSingle-cell transcriptomics reveals that, in mice and humans, a population of cells in the stromal vascular fraction of adipose tissue regulates adipogenesis by suppressing adipocyte formation in a paracrine manner.
- Petra C. Schwalie
- ,Hua Dong
- & Bart Deplancke
Article |
Blocking FSH induces thermogenic adipose tissue and reduces body fatAn antibody against the pituitary hormone Fsh reduces adiposity and increases thermogenesis in ovariectomized mice or mice fed a high-fat diet.
- Peng Liu
- ,Yaoting Ji
- & Mone Zaidi
Review Article |
Inflammation, metaflammation and immunometabolic disordersThe delicate balance between the immune system and metabolism, and its implications for obesity and metabolic disease are explored.
- Gökhan S. Hotamisligil
Brief Communications Arising |
Collingeet al. reply
- John Collinge
- ,Zane Jaunmuktane
- & Sebastian Brandner
Article |
Acetate mediates a microbiome–brain–β-cell axis to promote metabolic syndromeIncreased acetate production by an altered gut microbiota in rats fed a high-fat diet activates the parasympathetic nervous system, which in turn promotes increased insulin secretion, increased food intake, obesity and related changes.
- Rachel J. Perry
- ,Liang Peng
- & Gerald I. Shulman
Letter |
An obligatory role for neurotensin in high-fat-diet-induced obesityNeurotensin, a peptide expressed in the enteroendocrine cells of the small intestine that is released upon fat ingestion, is shown to increase fatty acid absorption, with neurotensin-deficient mice being protected from obesity induced by a high-fat diet.
- Jing Li
- ,Jun Song
- & B. Mark Evers
Letter |
Bidirectional electromagnetic control of the hypothalamus regulates feeding and metabolismActivation of glucose-sensing neurons in the ventromedial hypothalamic nucleus using radio waves or magnetic fields remotely and non-invasivelyin vivo increases plasma glucose and glucagon, and suppresses plasma insulin; conversely, remote inhibition of glucose-sensing neurons decreased blood glucose and increased plasma insulin.
- Sarah A. Stanley
- ,Leah Kelly
- & Jeffrey M. Friedman
Letter |
Transcriptional regulation of autophagy by an FXR–CREB axisThe FXR–CREB axis is identified as a key physiological switch that regulates autophagy during feeding/fasting cycles; in the fed state, the nuclear receptor FXR is shown to suppress autophagy in the liver by inhibiting autophagy-associated lipid breakdown triggered under fasting conditions by the transcriptional activator CREB.
- Sunmi Seok
- ,Ting Fu
- & Jongsook Kim Kemper
Letter |
Nutrient-sensing nuclear receptors coordinate autophagyThe nuclear receptors FXR and PPARα are shown to regulate autophagy by competing for binding to shared sites in the promoters of autophagic genes; in the fed state FXR suppresses hepatic autophagy, whereas in the fasted state PPARα is activated and reverses the normal suppression of autophagy.
- Jae Man Lee
- ,Martin Wagner
- & David D. Moore
Outlook |
Prevention: Air of dangerCarcinogens are all around us, so scientists are broadening their ideas of environmental risk.
- Rebecca Kessler
Review Article |
Cooperation between brain and islet in glucose homeostasis and diabetesAn alternative view of diabetes is presented in which blood glucose homeostasis is achieved via collective actions of two regulatory systems: a brain-centred glucoregulatory system (BCGS), which works together with the pancreatic islets; defects in both systems may be required for diabetes to occur, and interventions targeting both systems may have greater therapeutic potential.
- Michael W. Schwartz
- ,Randy J. Seeley
- & David D’Alessio
Obituary |
Wylie Walker Vale Jr(1941–2012)Endocrinologist who deduced the molecular structure of stress hormones.
- Ronald Evans
News |
Contraceptive risk of HIV long suspectedAnimal research showed 15 years ago that progesterone contraceptives could increase infections.
- Meredith Wadman
Letter |
Progesterone induces adult mammary stem cell expansionReproductive history influences breast cancer risk but the cellular mechanisms are unclear. Here it is shown that ovarian hormones regulate the size of the mammary stem cell pool in mice. The size of this pool increases when progesterone levels increase during the reproductive cycle. Progesterone probably regulates stem cell numbers through a paracrine mechanism involving induction of RANKL and Wnt in luminal cells.
- Purna A. Joshi
- ,Hartland W. Jackson
- & Rama Khokha
News & Views |
Cues from steroid hormonesThe steroid hormones oestrogen and progesterone have a role in sickness and in health. In breast tissue, both roles probably work through a single mechanism: controlling the number and activity of mammary stem cells.
- John P. Lydon
