Featured
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Article |
Quasi-experimental evaluation of a nationwide diabetes prevention programme
Analysis 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
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Article |
Mammary duct luminal epithelium controls adipocyte thermogenic programme
In 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
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Article
| Open AccessGDF15 promotes weight loss by enhancing energy expenditure in muscle
GDF15 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
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Article
| Open AccessPost-translational control of beige fat biogenesis by PRDM16 stabilization
The ubiquitin E3 ligase CUL2–APPBP2 determines PRDM16 protein stability by catalysing PRDM16 polyubiquitination in beige fat.
- Qiang Wang
- , Huixia Li
- & Shingo Kajimura
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Article |
Autoantibody mimicry of hormone action at the thyrotropin receptor
Cryo-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
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Article |
Maternal inheritance of glucose intolerance via oocyte TET3 insufficiency
Pregestational 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
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Article |
IL-27 signalling promotes adipocyte thermogenesis and energy expenditure
Therapeutic 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
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Article |
MC3R links nutritional state to childhood growth and the timing of puberty
MC3R 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
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Article |
Genetic insights into biological mechanisms governing human ovarian ageing
Hundreds 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
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Article |
Asymmetric activation of the calcium-sensing receptor homodimer
Cryo-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
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Article |
snRNA-seq reveals a subpopulation of adipocytes that regulates thermogenesis
Single-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
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Article |
A leptin–BDNF pathway regulating sympathetic innervation of adipose tissue
The 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
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Article |
Glucagon stimulates gluconeogenesis by INSP3R1-mediated hepatic lipolysis
A 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
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Article |
The structure of human thyroglobulin
The 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
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Article |
GDF15 mediates the effects of metformin on body weight and energy balance
In 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
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Review Article |
The integrative biology of type 2 diabetes
A Review of studies into insulin resistance and hepatic gluconeogenesis associated with obesity and type 2 diabetes.
- Michael Roden
- & Gerald I. Shulman
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Article |
Diabetes relief in mice by glucose-sensing insulin-secreting human α-cells
Islet 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
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Letter |
A stromal cell population that inhibits adipogenesis in mammalian fat depots
Single-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
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Article |
Blocking FSH induces thermogenic adipose tissue and reduces body fat
An 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
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Review Article |
Inflammation, metaflammation and immunometabolic disorders
The delicate balance between the immune system and metabolism, and its implications for obesity and metabolic disease are explored.
- Gökhan S. Hotamisligil
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Brief Communications Arising |
Collinge et al. reply
- John Collinge
- , Zane Jaunmuktane
- & Sebastian Brandner
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Article |
Acetate mediates a microbiome–brain–β-cell axis to promote metabolic syndrome
Increased 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
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Letter |
An obligatory role for neurotensin in high-fat-diet-induced obesity
Neurotensin, 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
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Letter |
Bidirectional electromagnetic control of the hypothalamus regulates feeding and metabolism
Activation of glucose-sensing neurons in the ventromedial hypothalamic nucleus using radio waves or magnetic fields remotely and non-invasively in 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
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Letter |
Transcriptional regulation of autophagy by an FXR–CREB axis
The 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
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Letter |
Nutrient-sensing nuclear receptors coordinate autophagy
The 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
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Outlook |
Prevention: Air of danger
Carcinogens are all around us, so scientists are broadening their ideas of environmental risk.
- Rebecca Kessler
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Review Article |
Cooperation between brain and islet in glucose homeostasis and diabetes
An 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
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Obituary |
Wylie Walker Vale Jr (1941–2012)
Endocrinologist who deduced the molecular structure of stress hormones.
- Ronald Evans
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News |
Contraceptive risk of HIV long suspected
Animal research showed 15 years ago that progesterone contraceptives could increase infections.
- Meredith Wadman
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Letter |
Progesterone induces adult mammary stem cell expansion
Reproductive 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
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News & Views |
Cues from steroid hormones
The 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