Metabolism articles within Nature Communications

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  • Article
    | Open Access

    Type 2 diabetes is associated with impaired wound healing, which can lead to limb loss. Here, the authors show that in Type 2 diabetic mouse models, Dnmt1 is upregulated in hematopoietic stem cells, leading to impaired differentiation towards macrophages, reduced macrophage infiltration in the wound and skewed M1/M2 polarization.

    • Jinglian Yan
    • , Guodong Tie
    •  & Louis M. Messina

  • Article
    | Open Access

    Activation of autophagy, via the transcription factor TFEB, is a promising strategy to treat metabolic diseases. Here, the authors report three novel classes of small molecules that promote TFEB nuclear translocation, and provide evidence for the therapeutic efficacy of these compounds in mice and worms.

    • Chensu Wang
    • , Hanspeter Niederstrasser
    •  & Michael A. White

  • Article
    | Open Access

    Spleen protein tyrosine kinase (Syk) has so far been mainly studied in haematopoietic and immune cells. Here, the authors show that Syk also has a role in brown adipose tissue, where it regulates the formation of brown adipocytes and their thermogenic activation in response to β-adrenergic stimulation.

    • Marko Knoll
    • , Sally Winther
    •  & Harvey F. Lodish

  • Article
    | Open Access

    Vps34 is a lipid kinase conserved from yeast to humans and involved in in intracellular vesicular trafficking and autophagy. Here Bilanges et al. show that inhibition of this kinase in mice improves glucose tolerance and diet-induced steatosis by modulating mitochondrial respiration and metabolism.

    • Benoit Bilanges
    • , Samira Alliouachene
    •  & Bart Vanhaesebroeck

  • Article
    | Open Access

    The APOE4 allele is the leading risk factor for late-onset Alzheimer’s disease, but how it might contribute to the disease is not clear. Here the authors show that a mouse expressing the human APOE4 allele displays hyperactivity in the entorhinal cortex due to a decreased inhibitory tone, which may in part explain accelerated Alzheimer’s pathology in APOE4 carriers.

    • Tal Nuriel
    • , Sergio L. Angulo
    •  & Karen E. Duff

  • Article
    | Open Access

    Dysregulation of insulin secretion dynamics plays a role in diabetes development. Here, the authors build a mathematical model of hepatic insulin signaling and propose a sequential model of post-meal control of glucose and lipids, according to which delayed aPKC suppression would contribute to selective hepatic insulin resistance.

    • Gang Zhao
    • , Dagmar Wirth
    •  & Michael Meyer-Hermann

  • Article
    | Open Access

    Pompe disease is caused by mutations in lysosomal acid α-glucosidase (GAA) and patients are being treated with recombinant human α-glucosidase (rhGAA). Here the authors present the crystal structures of rhGAA and its complexes with inhibitors and a pharmacological chaperone, which is important for drug development.

    • Véronique Roig-Zamboni
    • , Beatrice Cobucci-Ponzano
    •  & Gerlind Sulzenbacher

  • Article
    | Open Access

    Brown and beige adipose tissues dissipate heat via uncoupling protein 1 (UCP1). Here the authors show that the stress activated kinase MKK6 acts as a repressor of UCP1 expression, suggesting that its inhibition promotes adipose tissue browning and increases organismal energy expenditure.

    • Nuria Matesanz
    • , Edgar Bernardo
    •  & Guadalupe Sabio

  • Article
    | Open Access

    Current approaches to visualise brown adipose tissue (BAT) rely primarily on markers that reflect its metabolic activity. Here, the authors show that PD-L1 is expressed on brown adipocytes, does not change upon BAT activation, and that BAT volume in mice can be measured by PET-CT with a radiolabeled anti-PD-L1 antibody.

    • Jessica R. Ingram
    • , Michael Dougan
    •  & Hidde L. Ploegh

  • Article
    | Open Access

    HDAC3 is a critical mediator of hepatic lipid metabolism and its loss leads to fatty liver. Here, the authors characterize the liver HDAC3 interactome in vivo, provide evidence that HDAC3 interacts with PROX1, and show that HDAC3 and PROX1 control expression of genes regulating lipid homeostasis.

    • Sean M. Armour
    • , Jarrett R. Remsberg
    •  & Mitchell A. Lazar

  • Article
    | Open Access

    The misalignment between internal circadian rhythm and the day-night cycle can be caused by genetic, behavioural and environmental factors, and may have a profound impact on human physiology. Here West et al. show that desynchrony between the internal clock and the external environment alter metabolic parameters and cardiac function in mice.

    • Alexander C. West
    • , Laura Smith
    •  & David A. Bechtold

  • Article
    | Open Access

    The mechanistic link between metabolic stress and associated cardiomyopathy is unknown. Here the authors show that high fat diet causes calpain-1-dependent degradation of ERK5 leading to mitochondrial dysfunction, suggesting the maintenance of cardiac ERK5 as a therapeutic approach for cardiomyopathy prevention and/or treatment.

    • Wei Liu
    • , Andrea Ruiz-Velasco
    •  & Xin Wang

  • Article
    | Open Access

    Islet transplantation is considered one of the potential treatments for T1DM but limited islet survival and their impaired function pose limitations to this approach. Here Loh et al. show that the Y1 receptor is expressed in β- cells and inhibition of its signalling, both genetic and pharmacological, improves mouse and human islet function.

    • Kim Loh
    • , Yan-Chuan Shi
    •  & Herbert Herzog

  • Article
    | Open Access

    Obesity is an established risk factor for pancreatic ductal adenocarcinoma (PDA). Here the authors show that obesity induces the expression of the mitochondrial form of arginase ARG2 in PDA and that ARG2 silencing or loss results in ammonia accumulation and suppression of obesity-driven PDA tumor growth.

    • Tamara Zaytouni
    • , Pei-Yun Tsai
    •  & Nada Y. Kalaany

  • Article
    | Open Access

    The transcriptional co-activator Prdm16 regulates browning of white adipose tissue (WAT). Here, the authors show that Prdm16 interacts with the transcription factor Hlx, which is stabilized in response to β3-adrenergic signaling, to increase thermogenic gene expression and mitochondrial biogenesis in subcutaneous WAT.

    • Lei Huang
    • , Dongning Pan
    •  & Yong-Xu Wang

  • Article
    | Open Access

    The mechanism by which caffeine, an antagonist of adenosine receptors, regulates metabolism is not clear. Here the authors show that adenosine A1R receptor expression is increased in the hypothalamus of diet-induced obesity mice, and that body weight can be alleviated by central administration of caffeine via its action on hypothalamic oxytocin neurons.

    • Liufeng Wu
    • , Jia Meng
    •  & Guo Zhang

  • Article
    | Open Access

    Type 2 diabetes (T2D) is a heterogeneous disorder characterized by insulin resistance and impaired insulin secretion. Here Axelssonet al. show that Sox5, which is reduced in diabetes, regulates a set of differentially expressed genes in T2D and its genetic and pharmacological induction improves insulin secretion by diabetic islets.

    • A. S. Axelsson
    • , T. Mahdi
    •  & A. H. Rosengren

  • Article
    | Open Access

    Energy consumption in the brain is thought to respond to changes in neuronal activity, without informational role. Here the authors show that increased energy flux in the mushroom body, driven by a pair of input dopaminergic neurons, is a command for the formation of long-term memory in Drosophila.

    • Pierre-Yves Plaçais
    • , Éloïse de Tredern
    •  & Thomas Preat

  • Article
    | Open Access

    Lipid turnover in tissues can be calculated from ratios of different carbon isotopes. Here the authors use this approach to study lipid turnover in two distinct adipose tissue depots and find that, in obese individuals, visceral fat is more lipolytic than subcutaneous fat.

    • Kirsty L. Spalding
    • , Samuel Bernard
    •  & Peter Arner

  • Review Article
    | Open Access

    The brain controls peripheral glucose metabolism, for example by modulating hepatic gluconeogenesis or by regulating glucose uptake into brown adipose tissue. Here, the authors review the brain regions, neurons and molecular mechanisms involved in these processes, and discuss their relevance to disease.

    • Johan Ruud
    • , Sophie M. Steculorum
    •  & Jens C. Brüning

  • Article
    | Open Access

    Interleukin-6 (IL-6) is increased in obesity and activates T cells to promote inflammation. Here, Xuet al. use mice that lack IL-6 receptors on T cells to uncover the temporal and tissue-specific effects of classic and trans IL-6 signalling on inflammation and insulin resistance on a high-fat diet.

    • Elaine Xu
    • , Mafalda M. A. Pereira
    •  & Jens C. Brüning

  • Article
    | Open Access

    The factors that limit the nutrient flexibility of cells remain largely unknown. Here, the authors identify the glutamate/cysteine antiporter xCT in a genetic screen for glucose dependency and show it determines the ability of cells to survive under conditions of low glucose by limiting the utilization of glutamine.

    • Chun-Shik Shin
    • , Prashant Mishra
    •  & David C. Chan

  • Article
    | Open Access

    Activation of brown adipose tissue (BAT) reduces the development of atherosclerosis in animal models. Here the authors show that BAT activation also increases reverse cholesterol transport and turnover of high-density lipoprotein, which likely contributes to the anti-atherosclerotic effect of BAT activation.

    • Alexander Bartelt
    • , Clara John
    •  & Joerg Heeren

  • Article
    | Open Access

    LDL receptor-related protein 1 (LRP1) is an endocytic receptor involved in cell signalling and energy homeostasis. Here Maoet al. demonstrate that endothelial Lrp1 modulates lipid and glucose metabolism by binding the nuclear receptor Pparγ and promoting its transcriptional activity.

    • Hua Mao
    • , Pamela Lockyer
    •  & Xinchun Pi

  • Article
    | Open Access

    Steviol glycosides are sweet-tasting compounds isolated from a South American shrub and are increasingly used as sweeteners in foods and beverages. Philippaertet al. demonstrate that steviol glycosides potentiate Ca2+-dependent TRPM5 activity and promote glucose-induced insulin secretion and glucose tolerance.

    • Koenraad Philippaert
    • , Andy Pironet
    •  & Rudi Vennekens

  • Article
    | Open Access

    De novo lipogenesis is tightly controlled by hormonal and nutritional signals and plays an important role in energy homoeostasis. Here, Liu et al. show that zinc finger protein ZBTB20 regulates the expression of key glycolytic and lipogenic genes by modulating ChREBP expression and transcriptional activity.

    • Gan Liu
    • , Luting Zhou
    •  & Weiping J. Zhang

  • Article
    | Open Access

    The enzyme Atgl participates in the breakdown of lipids in adipose tissue. Here the authors show that pharmacological inhibition of Atgl reduces weight gain and improves metabolic health in mice fed a high-fat diet, without causing adverse effects in cardiac muscle associated with genetic depletion ofAtgl.

    • Martina Schweiger
    • , Matthias Romauch
    •  & Rudolf Zechner

  • Article
    | Open Access

    Nrf2 regulates oxidative and electrophilic stress responses by modulating the expression of enzymes involved in detoxification pathways. Here Suzukiet al. show that Nrf2 activation in early tubular development promotes nephrogenic diabetes insipidus by regulating aquaporin 2 expression and trafficking and water permeability.

    • Takafumi Suzuki
    • , Shiori Seki
    •  & Masayuki Yamamoto

  • Article
    | Open Access

    Unlike males, female mice are resistant to hypothalamic inflammation and weight gain when fed a high-fat diet. Here, the authors reveal sex-specific regulation of hypothalamic microglial activation through CX3CR1 signalling, providing a potential mechanism for differential susceptibility to diet-induced obesity.

    • Mauricio D. Dorfman
    • , Jordan E. Krull
    •  & Joshua P. Thaler

  • Article
    | Open Access

    The kinase FAK is important for integrin signalling and promotes cell survival. Here, the authors demonstrate FAK regulates adipocyte survival, and is particularly important for maintaining insulin sensitivity during adipose tissue expansion in the context of a calorie-rich diet.

    • Cynthia T. Luk
    • , Sally Yu Shi
    •  & Minna Woo

  • Article
    | Open Access

    Brown adipose tissue (BAT) takes up and burns fatty acids for thermogenesis in mice. Here the authors use PET to show that, in humans, cold stimulation increases BAT dietary fatty acid uptake from plasma and oxidative metabolism, although, unlike mice, human BAT takes up less fatty acids than other metabolic tissues.

    • Denis P. Blondin
    • , Hans C. Tingelstad
    •  & André C. Carpentier

  • Article
    | Open Access

    Global warming is expected to lead to shifts in species' geographic ranges to track preferred temperatures. Here, the authors show that populations of the common periwinkle vary in their sensitivity to ocean acidification, another major global change driver, which could further restrict range shifts caused by warming.

    • Piero Calosi
    • , Sedercor Melatunan
    •  & Simon D. Rundle

  • Article
    | Open Access

    Feeding control requires the integration and coordination of motivational, sensory and motor circuits in the brain. Here, the authors discover a set of neurons that regulate feeding inDrosophilaby promoting insulin release, and whose activity reflects physiological hunger and satiety states of flies.

    • Yin Peng Zhan
    • , Li Liu
    •  & Yan Zhu

  • Article
    | Open Access

    Diabetes is characterized by prolonged hyperglycaemia and tissue damage in pancreatic islets. Here, Brereton et al. show that chronic high glucose levels lead to glycogen accumulation in β-cells, associated with reduced autophagy, impaired metabolism, insulin granule depletion and apoptosis.

    • Melissa F. Brereton
    • , Maria Rohm
    •  & Frances M. Ashcroft

  • Article
    | Open Access

    Ventricular arrhythmia is a leading cause of death in patients with diabetes. Here the authors show that inflammasome activation and ILK-1β production in cardiac macrophages cause arrhythmia in diabetic mice, which can be successfully treated using agonists to IL-1β receptor or NLRP3 inhibitors.

    • Gustavo Monnerat
    • , Micaela L. Alarcón
    •  & Emiliano Medei

  • Article
    | Open Access

    Glycine sensing in the dorsal vagal complex (DVC) regulates hepatic glucose production in rodents. Here the authors show that pharmacological and molecular inhibition of glycine reuptake in the DVC potentiates NMDA receptors, and improves metabolic homeostasis in animal models of obesity and diabetes.

    • Jessica T. Y. Yue
    • , Mona A. Abraham
    •  & Tony K. T. Lam

  • Article
    | Open Access

    GPR120 is a G-protein-coupled receptor that binds polyunsaturated fatty acids. Here, the authors show that GPR120 is upregulated in brown fat in cold-exposed mice, and mediates thermogenic activation of brown fat via a mechanism that, at least in part, depends on the release of the adipokine FGF21.

    • Tania Quesada-López
    • , Rubén Cereijo
    •  & Francesc Villarroya

  • Article
    | Open Access

    Mice deficient in the pro-inflammatory cytokine IFNγ have improved glucose tolerance. Here, the authors show that this effect depends on the gut microbeAkkermansia muciniphila, whose abundance increases in the absence IFNγ, and which is known to have beneficial effects on host metabolism.

    • Renee L. Greer
    • , Xiaoxi Dong
    •  & Natalia Shulzhenko

  • Article
    | Open Access

    Raising cellular levels of the metabolic cofactor NAD+ reverses key indicators of aging. Here, Ratajczak et al. show that cellular levels of NAD+ depend on the extracellular catalytic activity of NRK1, which processes two NAD+precursors, nicotinamide mononucleotide and nicotinamide riboside, in mice.

    • Joanna Ratajczak
    • , Magali Joffraud
    •  & Carles Cantó

  • Article
    | Open Access

    NAD+ is an important coenzyme that mediates cellular metabolism and defends against stresses due to age and overnutrition. Here the authors demonstrate unique bioavailability of the NAD+ precursor vitamin nicotinamide riboside (NR) in mice and humans, and show that NR safely elevates human NAD+.

    • Samuel A. J. Trammell
    • , Mark S. Schmidt
    •  & Charles Brenner

  • Article
    | Open Access

    Obesity is associated with higher breast cancer risk and poor prognosis. Here, the authors show that obesity promotes breast cancer through the recruitment of macrophages with activated NLRC4 inflammasome, which activate IL-1β production, resulting in VEGFA expression in adipocytes and angiogenesis.

    • Ryan Kolb
    • , Liem Phan
    •  & Weizhou Zhang

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