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microRNA-33 controls hunger signaling in hypothalamic AgRP neurons

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  • Nathan L. Price

    (Yale University School of Medicine
    Yale University School of Medicine
    Yale Center for Molecular and System Metabolism. Yale University School of Medicine
    Translational Gerontology Branch, National Institute on Aging, National Institutes of Health)

  • Pablo Fernández-Tussy

    (Yale University School of Medicine
    Yale University School of Medicine
    Yale Center for Molecular and System Metabolism. Yale University School of Medicine)

  • Luis Varela

    (Yale University School of Medicine
    Yale Center for Molecular and System Metabolism. Yale University School of Medicine
    Laboratory of Glia -Neuron Interactions in the control of Hunger. Achucarro Basque Center for Neuroscience
    Basque Foundation for Science)

  • Magdalena P. Cardelo

    (Yale University School of Medicine
    Yale University School of Medicine
    Yale Center for Molecular and System Metabolism. Yale University School of Medicine)

  • Marya Shanabrough

    (Yale University School of Medicine)

  • Binod Aryal

    (Yale University School of Medicine
    Yale University School of Medicine
    Yale Center for Molecular and System Metabolism. Yale University School of Medicine)

  • Rafael Cabo

    (Translational Gerontology Branch, National Institute on Aging, National Institutes of Health)

  • Yajaira Suárez

    (Yale University School of Medicine
    Yale University School of Medicine
    Yale Center for Molecular and System Metabolism. Yale University School of Medicine
    Department of Pathology. Yale University School of Medicine)

  • Tamas L. Horvath

    (Yale University School of Medicine
    Yale Center for Molecular and System Metabolism. Yale University School of Medicine
    Laboratory of Glia -Neuron Interactions in the control of Hunger. Achucarro Basque Center for Neuroscience
    Basque Foundation for Science)

  • Carlos Fernández-Hernando

    (Yale University School of Medicine
    Yale University School of Medicine
    Yale Center for Molecular and System Metabolism. Yale University School of Medicine
    Department of Pathology. Yale University School of Medicine)

Abstract

AgRP neurons drive hunger, and excessive nutrient intake is the primary driver of obesity and associated metabolic disorders. While many factors impacting central regulation of feeding behavior have been established, the role of microRNAs in this process is poorly understood. Utilizing unique mouse models, we demonstrate that miR-33 plays a critical role in the regulation of AgRP neurons, and that loss of miR-33 leads to increased feeding, obesity, and metabolic dysfunction in mice. These effects include the regulation of multiple miR-33 target genes involved in mitochondrial biogenesis and fatty acid metabolism. Our findings elucidate a key regulatory pathway regulated by a non-coding RNA that impacts hunger by controlling multiple bioenergetic processes associated with the activation of AgRP neurons, providing alternative therapeutic approaches to modulate feeding behavior and associated metabolic diseases.

Suggested Citation

  • Nathan L. Price & Pablo Fernández-Tussy & Luis Varela & Magdalena P. Cardelo & Marya Shanabrough & Binod Aryal & Rafael Cabo & Yajaira Suárez & Tamas L. Horvath & Carlos Fernández-Hernando, 2024. "microRNA-33 controls hunger signaling in hypothalamic AgRP neurons," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-46427-0
    DOI: 10.1038/s41467-024-46427-0
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    References listed on IDEAS

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    1. Takahiro Horie & Tetsushi Nakao & Yui Miyasaka & Tomohiro Nishino & Shigenobu Matsumura & Fumiko Nakazeki & Yuya Ide & Masahiro Kimura & Shuhei Tsuji & Randolph Ruiz Rodriguez & Toshimitsu Watanabe & , 2021. "microRNA-33 maintains adaptive thermogenesis via enhanced sympathetic nerve activity," Nature Communications, Nature, vol. 12(1), pages 1-17, December.
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