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MicroRNA-7 regulates melanocortin circuits involved in mammalian energy homeostasis

Author

Listed:
  • Mary P. LaPierre

    (Institute of Molecular Health Sciences, ETH Zürich)

  • Katherine Lawler

    (Wellcome Trust-MRC Institute of Metabolic Science, Addenbrooke’s Hospital)

  • Svenja Godbersen

    (Institute of Molecular Health Sciences, ETH Zürich)

  • I. Sadaf Farooqi

    (Wellcome Trust-MRC Institute of Metabolic Science, Addenbrooke’s Hospital)

  • Markus Stoffel

    (Institute of Molecular Health Sciences, ETH Zürich
    University of Zürich)

Abstract

MicroRNAs (miRNAs) modulate physiological responses by repressing the expression of gene networks. We found that global deletion of microRNA-7 (miR-7), the most enriched miRNA in the hypothalamus, causes obesity in mice. Targeted deletion of miR-7 in Single-minded homolog 1 (Sim1) neurons, a critical component of the hypothalamic melanocortin pathway, causes hyperphagia, obesity and increased linear growth, mirroring Sim1 and Melanocortin-4 receptor (MC4R) haplo-insufficiency in mice and humans. We identified Snca (α-Synuclein) and Igsf8 (Immunoglobulin Superfamily Member 8) as miR-7 target genes that act in Sim1 neurons to regulate body weight and endocrine axes. In humans, MIR-7-1 is located in the last intron of HNRNPK, whose promoter drives the expression of both genes. Genetic variants at the HNRNPK locus that reduce its expression are associated with increased height and truncal fat mass. These findings demonstrate that miR-7 suppresses gene networks involved in the hypothalamic melanocortin pathway to regulate mammalian energy homeostasis.

Suggested Citation

  • Mary P. LaPierre & Katherine Lawler & Svenja Godbersen & I. Sadaf Farooqi & Markus Stoffel, 2022. "MicroRNA-7 regulates melanocortin circuits involved in mammalian energy homeostasis," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-33367-w
    DOI: 10.1038/s41467-022-33367-w
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    References listed on IDEAS

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