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  • The mechanisms that drive cancer cachexia are unclear. Adipocyte activation of GPR81 by high levels of lactate is now shown to drive adipose tissue browning, thermogenesis and a loss of body weight in mouse models of cancer.

    • Jack D. Sanford
    • Marcus D. Goncalves
    News & Views
  • The mechanism by which metformin affects food intake remains controversial. Now, two studies link metformin treatment with the induction of the appetite-suppressing metabolite N-lactoyl-phenylalanine, which is produced by the intestine.

    • Tara TeSlaa
    News & Views
  • Eating requires the sensing in the stomach of not only nutrients, but also volume. A study in Nature Metabolism shows that stretch activation of PIEZO1 on X/A-like cells of the stomach reduces ghrelin production and secretion, which consequently reduces food intake.

    • Choi Sang Daniel Lam
    • M. Maya Kaelberer
    News & Views
  • Sharma et al. review the regulation and biological functions of apparently ‘futile’ dynamic lipid cycle in regulating whole-body metabolic homeostasis.

    • Anand Kumar Sharma
    • Radhika Khandelwal
    • Christian Wolfrum
    Review Article
  • A recent study in Nature Metabolism uncovers a mechanism for pain sensitization that involves a regulatory protein of glycogen metabolism in spinal astrocytes. Targeting this protein, or the lactate fluxes linked to glycogen breakdown, may provide novel opportunities for pain management.

    • Carlos Manlio Díaz-García
    News & Views
  • The authors present a holistic view of factors that drive the increasing burden of obesity in Latin America.

    • Sandra Roberta G. Ferreira
    • Yazmín Macotela
    • Marcelo A. Mori
    Review Article
  • In this study in humans, the authors describe distinct phases of adaptions in the plasma proteome to seven days without food, and identify limited associations of protein changes with weight loss.

    • Benjamin D. Horne
    News & Views
  • In this issue of Nature Metabolism, it is shown that the abundance of Caenorhabditis elegans branched-chain aminotransferase-1 (BCAT-1) — which catalyses the first step of branched-chain amino acid (BCAA) catabolism — declines sharply in aged wild-type nematodes but not in slowly ageing mutants, and that stimulating BCAA catabolism extends reproductive longevity.

    • Leah E. Jamerson
    • Patrick C. Bradshaw
    News & Views
  • The microbiome is implicated in a study that involves the metabolism of dietary fibre into short-chain fatty acids, which provides a biochemical link to the poorly understood histone butyrylation.

    • Yudong Sun
    • Jason W. Locasale
    News & Views
  • Resistant starch is a prebiotic fibre that is fermented by the gut microbiota and leads to benefits for host physiology. A clinical trial in Nature Metabolism demonstrates weight loss when resistant starch was given to individuals with excess weight.

    • Matthew M. Carter
    • Sean P. Spencer
    News & Views
  • Individuals with osteoporosis have increased risk of Alzheimer’s disease or cognitive impairment during ageing. We elucidated a partial explanation for bone dysmetabolism’s association with such cognitive decline, by demonstrating how elevated sclerostin secretion from osteocytes in bone impaired cognitive function in aged mice and in an Alzheimer’s disease mouse model.

    Research Briefing
  • The immunosuppressive metabolic tumour microenvironment in solid tumours limits the antitumour activity of cell-based immunotherapy. In this Perspective, McPhedran et al. propose a framework to overcome this issue by engineering metabolic networks in T cells to enhance chimeric antigen receptor T cell efficiency

    • Sarah J. McPhedran
    • Gillian A. Carleton
    • Julian J. Lum
    Perspective
  • Succinate can be released from contracting skeletal muscle and accumulate in brown adipose tissue (BAT) to drive thermogenesis and protect against obesity. A study in this issue of Nature Metabolism uncovers the mechanistic underpinnings of BAT succinate sequestration through MCT1-dependent uptake and cytosolic pH changes, thus strengthening the role for cellular shuttling of succinate in the control of systemic energy homeostasis.

    • Jens Lund
    • Marie Sophie Isidor
    • Zachary Gerhart-Hines
    News & Views
  • Hypothalamic neural pathways control appetite and food intake, and thereby influence body weight and metabolism. De Solis et al. apply chemogenetics to simultaneously manipulate two subpopulations of hypothalamic neurons. Using this approach, the authors identify a pathway that regulates feeding behaviour.

    • Liangyou Rui
    News & Views
  • Although obesity is associated with higher risk of cardiometabolic disease, high-protein diets can reduce fatness but still promote cardiometabolic disease. Zhang et al. address this contradiction and show that high-protein diets, and subsequently higher blood leucine levels, promote mTORC1 activation in macrophages in humans and mice, and that an increase in dietary leucine raises the risk of atherosclerosis in a mouse model.

    • Adam J. Rose
    • Patricia M. Rusu
    News & Views
  • Selenium is usually incorporated into selenoproteins, with important functions in redox regulation. A new study in Nature Metabolism reveals a previously unappreciated role for selenium-based chemical species as direct electron donors to reduce ubiquinone, thus contributing to redox homeostasis by preventing lipid peroxidation.

    • Ian G. Chambers
    • Rajiv R. Ratan
    News & Views
  • High-fat diet (HFD) causes mitochondrial dysfunction in white adipocytes. A study in Nature Metabolism identifies the small GTPase RalA as a culprit in mice. Upon HFD, RalA activates the fission protein Drp1 to cause mitochondrial fragmentation and dysfunction, linking mitochondrial fuel utilization in white adipocytes to systemic lipid metabolism.

    • Ludovica Zambello
    • Luca Scorrano
    News & Views
  • Here, we reveal functional heterogeneity among β cells and discover that readily releasable β cells (RRβs) are a subpopulation that disproportionally contributes to biphasic glucose-stimulated insulin secretion. We further show that the dysfunction of RRβs has a crucial role in the progression of diabetes.

    Research Briefing
  • Demicco, Liu et al. discuss how metabolic adaptations in cancer contribute to tumour progression. These adaptations entail high spatial and temporal metabolic heterogeneity, based on local adaptations in different regions of the tumour microenvironment, as well as metabolic evolution over time as the tumour progresses and metastasizes.

    • Margherita Demicco
    • Xiao-Zheng Liu
    • Sarah-Maria Fendt
    Review Article