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Volume 6 Issue 3, March 2024

Bone-to-brain crosstalk

Bone-derived sclerostin accelerates the progression of Alzheimer’s disease (AD) by deregulating the Wnt–β-catenin signalling pathway in the brain. The image is a staining of the enzyme β-secretase (essential for AD pathogenesis) in a hippocampus section from a mouse model of AD.

See Shi et al.

Image: Baosheng Guo, Nanjing University. Cover Design: Thomas Phillips.

Editorial

  • When preparing your manuscript, clear presentation of the data and concise writing are key. In this Editorial, we offer tips on how to better communicate your results.

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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
  • 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
  • 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
  • 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
  • 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
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Research Briefings

  • AMPK directly phosphorylates the mitochondrial protein SYNJ2BP to facilitate its interaction with the RNA-binding protein SYNJ2a, which transports Pink1 mRNA into neurites. AMPK inhibition downstream of insulin signalling untethers Pink1 mRNA from neuronal mitochondria and favours PINK1-dependent mitophagy in neurons. ApoE4-induced insulin receptor internalization reverses the process by stabilizing Pink1 mRNA binding to neuronal mitochondria.

    Research Briefing
  • 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.

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Reviews

  • 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
  • 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
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