Metabolism articles within Nature Communications

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  • Article
    | Open Access

    Understanding the pH changes at cell surfaces is important for understanding the mechanisms of different physiological processes. Here, the authors report on the development of a cell membrane anchored gold nanoparticle for surface enhanced Raman spectroscopy determination of pH.

    • Leonardo Puppulin
    • , Shigekuni Hosogi
    •  & Yoshinori Marunaka

  • Article
    | Open Access

    The molecular pathway(s) driving antipsychotics (AP) induced hyperphagia remains unclear. A novel C. elegans system is used here to screen for FDA approved drugs that selectively suppresses this response, unraveling potential molecular mediators influencing AP induced hyperphagia in mouse models.

    • Anabel Perez-Gomez
    • , Maria Carretero
    •  & Michael Petrascheck

  • Article
    | Open Access

    Endocannabinoid signaling regulates food intake and is a potential therapeutic target for obesity. Here the authors show that adipocyte O-GlcNAc transferase (OGT) is required for high fat diet-induced hyperphagia via transcriptional activation of de novo lipid desaturation and accumulation of an endogenous appetite-inducing cannabinoid.

    • Min-Dian Li
    • , Nicholas B. Vera
    •  & Xiaoyong Yang

  • Article
    | Open Access

    Assessing biological circuit connections in single cells has been intractable due to lack of appropriate tools. Here, Bleck et al. develop a method to assess mitochondrial network connectivity in muscle cells and observe clear differences consistent with differing energy requirements.

    • Christopher K. E. Bleck
    • , Yuho Kim
    •  & Brian Glancy

  • Article
    | Open Access

    No effective pharmacological treatments exist for nonalcoholic fatty liver disease (NAFLD). Here, the authors show that serotonin concentration in the portal blood is increased in nine human subjects and in mice fed a high-fat diet, and that local serotonin signaling ablation, either genetically or with an antagonist, prevents hepatic steatosis in mice.

    • Wonsuk Choi
    • , Jun Namkung
    •  & Hail Kim

  • Article
    | Open Access

    Gluten-free diets are increasingly common in the general population. Here, the authors report the results of a randomised cross-over trial involving middle-aged, healthy Danish adults, showing evidence that a low-gluten diet leads to gut microbiome changes, possibly due to variations in dietary fibres.

    • Lea B. S. Hansen
    • , Henrik M. Roager
    •  & Oluf Pedersen

  • Article
    | Open Access

    Uptake and release of glycerol from the small intestine and adipocytes is facilitated by a subclass of aquaporins (AQP), but how glycerol flow is regulated remains poorly understood. Here authors solve the crystal structure of AQP10 and show how lipolysis is coupled to AQP10 regulation in

    • Kamil Gotfryd
    • , Andreia Filipa Mósca
    •  & Pontus Gourdon

  • Article
    | Open Access

    Excess caloric intake leads to increased thermogenesis in brown adipose tissue, to limit weight gain. Here, the authors show that neuropeptide FF receptor-2 signalling promotes thermogenesis via control of NPY expression in the arcuate nucleus, and that it absence in mice leads to a failure of activation of diet-induced thermogenesis and the development of exacerbated obesity.

    • Lei Zhang
    • , Chi Kin Ip
    •  & Herbert Herzog

  • 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

    Organisms could respond to essential resource limitation by increasing metabolic efficiency or resource acquisition ability. Here, the authors experimentally evolve green algae under different resource limitations and show convergent evolution of core metabolism rather than resource specialization.

    • Manu Tamminen
    • , Alexander Betz
    •  & Anita Narwani

  • Article
    | Open Access

    Increased glycolysis and inflammatory responses have been observed in endothelial cells exposed to disturbed flow. However, the role of endothelial glycolysis in atherosclerosis is unclear. Here the authors unveil a protective role for glycolysis by showing that endothelial deletion of Prkaa1 accelerates atherosclerosis in hyperlipidemic mice through a reduction of glycolytic metabolism.

    • Qiuhua Yang
    • , Jiean Xu
    •  & Yuqing Huo

  • 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

    Tobacco smoking and cold exposure are environmental modulators of human energy metabolism suppressing appetite and increasing energy expenditure, respectively. Here, the authors develop a novel pharmacological strategy in which they simultaneously mimic the metabolic benefits of both phenomena through small-molecule combination therapy, and show that this treatment improves metabolic health of obese mice.

    • Christoffer Clemmensen
    • , Sigrid Jall
    •  & Matthias H. Tschöp

  • Article
    | Open Access

    Metabolic reprogramming of smooth muscle cells (SMCs) plays an important role in the pathogenesis of pulmonary arterial hypertension (PAH). Here, Dai et al. show that the glycolytic enzyme alpha-enolase contributes to this reprogramming, and that its inhibition limits SMC proliferation and disease progression in animal models of PAH.

    • Jingbo Dai
    • , Qiyuan Zhou
    •  & Guofei Zhou

  • Article
    | Open Access

    The role of the gut microbiota in hepatic lipid metabolism is controversial and incompletely understood. Here the authors perform multi-omics analyses of altered lipid metabolic processes in germ-free and specific pathogen-free mice, revealing how the gut microbiota affects hepatic fatty acid desaturation and elongation.

    • Alida Kindt
    • , Gerhard Liebisch
    •  & Josef Ecker

  • Article
    | Open Access

    Brown adipose tissue (BAT) thermogenesis counteracts obesity and promotes metabolic health. The role of long non-coding RNAs (lncRNAs) in the regulation of this process is not well understood. Here the authors identify a maternally expressed lncRNA, H19, that increases BAT oxidative metabolism and energy expenditure.

    • Elena Schmidt
    • , Ines Dhaouadi
    •  & Jan-Wilhelm Kornfeld

  • Article
    | Open Access

    Common genetic variants associated with plasma lipids have been extensively studied for a better understanding of common diseases. Here, the authors use whole-genome sequencing of 16,324 individuals to analyze rare variant associations and to determine their monogenic and polygenic contribution to lipid traits.

    • Pradeep Natarajan
    • , Gina M. Peloso
    •  & Sebastian Zoellner

  • Article
    | Open Access

    Ceramides are signalling molecules that regulate several physiological functions including insulin sensitivity. Here the authors report a selective ceramide synthase 1 inhibitor that counteracts lipid accumulation within the muscle and adiposity by increasing fatty acid oxidation but without affecting insulin sensitivity in mice fed with an obesogenic diet.

    • Nigel Turner
    • , Xin Ying Lim
    •  & Anthony S. Don

  • Review Article
    | Open Access

    Gut microbial metabolites are known to impact many physiological processes of the host and play a critical role in immune-homeostasis. Here the authors review our current understanding and appreciation of the importance of microbially derived tryptophan catabolites during both health and disease.

    • Henrik M. Roager
    •  & Tine R. Licht

  • Article
    | Open Access

    Dietary fatty acids have different effects on human health. Here, the authors show that ingestion of the fatty acid C18:0, but not of C16:0, rapidly leads to fusion of mitochondria and fatty acid oxidation in humans, possibly explaining the health benefits of C18:0.

    • Deniz Senyilmaz-Tiebe
    • , Daniel H. Pfaff
    •  & Aurelio A. Teleman

  • Article
    | Open Access

    Pulmonary alveolar proteinosis (PAP) is associated with defective macrophage clearance of surfactant. Here, the authors show that patients with PAP have altered cholesterol-to-phospholipid ratio in their surfactant, and that more importantly, statin therapy and reduction of cholesterol accumulation in macrophages can ameliorate PAP in both humans and mice.

    • Cormac McCarthy
    • , Elinor Lee
    •  & Bruce C. Trapnell

  • Article
    | Open Access

    Cholesterol homeostasis can modulate immunity via multiple pathways. Here the authors show that apolipoprotein E, an important regulator of cholesterol, produced by myeloid cells can regulate T cell activation by controlling the antigen presentation activity of dendritic cells in both humans and mice.

    • Fabrizia Bonacina
    • , David Coe
    •  & Giuseppe D. Norata

  • Article
    | Open Access

    Hypertrophic cardiomyocytes switch their metabolism from fatty acid oxidation to glucose use, but the functional role of this change is unclear. Here the authors show that high intracellular glucose inhibits the degradation of branched-chain amino acids, which is required for the activation of pro-growth mTOR signaling.

    • Dan Shao
    • , Outi Villet
    •  & Rong Tian

  • Article
    | Open Access

    Antibiotic-induced microbiome depletion is one of the most common approaches to modulate the gut microbiome. Here the authors demonstrate that it affects gut homeostasis and glucose metabolism by decreasing luminal short chain fatty acids and leading to a shift of energy utilization by colonocytes.

    • Amir Zarrinpar
    • , Amandine Chaix
    •  & Satchidananda Panda

  • Article
    | Open Access

    Circulating lipoprotein(a) is an important risk factor for cardiovascular disease and shows variability between different ethnic groups. Here, Zekavat et al. perform whole-genome sequencing in individuals of European and African ancestries and find ancestry-specific genetic determinants for lipoprotein(a) levels.

    • Seyedeh M. Zekavat
    • , Sanni Ruotsalainen
    •  & Sebastian Zoellner

  • Article
    | Open Access

    FXR plays an important role in bile acid homeostasis by transcriptionally modulating several enterohepatic genes, including intestinal FGF19, that repress hepatic bile acid synthesis. Here the authors show that postprandial FGF19 regulates FXR transcriptional activity via its action on the tyrosine kinase Src, which phosphorylates FXR.

    • Sangwon Byun
    • , Dong-Hyun Kim
    •  & Jongsook Kim Kemper

  • 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

    Insulin secretion by β-cells is stimulated by glucose and is dependent on the induction of β-cell membrane depolarization, mainly driven by the closure of KATP channels, which in turn promotes voltage-gated Ca2+ channel opening. Here the authors show that LRRC8 volume-regulated anion channels (VRACs) modulate glucose-stimulated calcium increase and insulin secretion.

    • Till Stuhlmann
    • , Rosa Planells-Cases
    •  & Thomas J. Jentsch

  • Article
    | Open Access

    Non-invasive techniques to assess the progression of type 1 diabetes prior to clinical onset are needed. Here the authors apply a contrast-enhanced ultrasound measurement of mouse pancreatic blood flow to detect changes in the islet microvasculature that undergoes rearrangements during diabetes and predict disease progression.

    • Joshua R. St Clair
    • , David Ramirez
    •  & Richard K. P. Benninger

  • Article
    | Open Access

    GPR40 is a G-protein coupled receptor that binds to free fatty acids, mediating insulin and incretin secretion. Here, the authors present the crystal structure of human GPR40 with an agonist bound to an allosteric site located near the lipid-rich region that suggests a mechanism for biased agonism.

    • Joseph D. Ho
    • , Betty Chau
    •  & Chafiq Hamdouchi

  • Article
    | Open Access

    JMJD1A is essential for thermogenic gene induction in brown adipose tissue. Here the authors show that white adipose tissue beige-ing requires both β-adrenergic-dependent phosphorylation of S265 and demethylation activity of JMJD1A while brown adipose tissue-driven thermogenesis requires β-adrenergic dependent phosphorylation of S265 but is independent of H3K9me2 demethylation.

    • Yohei Abe
    • , Yosuke Fujiwara
    •  & Juro Sakai

  • 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

  • Article
    | Open Access

    Iron homeostasis dysfunctions have been associated with several metabolic disorders including obesity, steatosis and diabetes. Here the authors demonstrate that the hepcidin repressor matriptase-2 regulates adiposity and its deficiency protects mice against obesity and promotes lipolysis.

    • Alicia R. Folgueras
    • , Sandra Freitas-Rodríguez
    •  & Carlos López-Otín

  • Article
    | Open Access

    Nucleolar stress can disrupt ribosome biogenesis and in turn energy metabolism and lipid storage, but how this is regulated is unclear. Here, the authors show in C. elegans that the transcription factor PHA-4/FOXA acts as a sensor for nucleolar stress and can regulate expression of lipogenic genes

    • Jieyu Wu
    • , Xue Jiang
    •  & Bin Liang

  • Article
    | Open Access

    High protein diets are known to improve metabolic parameters including adiposity and glucose homeostasis. Here the authors demonstrate that preabsorptive upper small intestinal protein-sensing mechanisms mediated by peptide transporter 1 improve glucose homeostasis by inhibiting hepatic glucose production.

    • Helen J. Dranse
    • , T. M. Zaved Waise
    •  & Tony K. T. Lam

  • Article
    | Open Access

    Polycystic kidney disease (PKD) is characterized by the formation of large fluid-filled cysts. Here Flowers and colleagues show that loss of Lkb1, downregulated in PKD, renders kidney cells dependent on glutamine for growth, and suggest that inhibition of glutamine metabolism may prevent cyst development in PKD.

    • Ebony M. Flowers
    • , Jessica Sudderth
    •  & Thomas J. Carroll

  • Article
    | Open Access

    Obesity can affect bone marrow cell differentiation and the generation of myeloid and lymphoid cells. Here, the authors show that diet and obesity, as well as low-dose lipopolysaccharide, can alter Toll-like receptor 4 signaling bone marrow cells to skew the myeloid-lymphoid homeostasis in mice.

    • Ailing Liu
    • , Minhui Chen
    •  & Lisa Borghesi

  • Article
    | Open Access

    Glucagon secretion is promoted during hypoglycemia and inhibited by increased glucose levels. Here, Basco et al. show that glucokinase suppresses glucose-regulated glucagon secretion by modulating the intracellular ATP/ADP ratio and the closure of KATP channels in α-cells.

    • Davide Basco
    • , Quan Zhang
    •  & Bernard Thorens

  • Article
    | Open Access

    Methyl metabolites in the one-carbon cycle, such as phosphatidylcholines and S-adenosylmethionine, play a role in hepatic triglyceride regulation. Here Kim et al. show that AhR and SHP are both involved in the expression of several key enzymes of one-carbon metabolism, with the former regulating them early after feeding and the latter inhibiting AhR at later stages.

    • Young-Chae Kim
    • , Sunmi Seok
    •  & Jongsook Kim Kemper

  • Article
    | Open Access

    White adipose tissue can undergo a process of beiging and acquire functional characteristics similar to brown adipose tissue, including the ability to dissipate energy via uncoupled respiration. Here, Velazquez-Villegas et al. show that activation of the bile acid membrane receptor, TGR5, leads to white adipocyte beiging by promoting mitochondrial fission.

    • Laura A. Velazquez-Villegas
    • , Alessia Perino
    •  & Kristina Schoonjans

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