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A fatty acid-dependent hypothalamic–DVC neurocircuitry that regulates hepatic secretion of triglyceride-rich lipoproteins

Author

Listed:
  • Jessica T. Y. Yue

    (UHN)

  • Mona A. Abraham

    (UHN
    University of Toronto)

  • Mary P. LaPierre

    (UHN
    University of Toronto)

  • Patricia I. Mighiu

    (UHN
    University of Toronto)

  • Peter E. Light

    (University of Alberta)

  • Beatrice M. Filippi

    (UHN)

  • Tony K. T. Lam

    (UHN
    University of Toronto
    University of Toronto
    Banting and Best Diabetes Centre, University of Toronto)

Abstract

The brain emerges as a regulator of hepatic triglyceride-rich very-low-density lipoproteins (VLDL-TG). The neurocircuitry involved as well as the ability of fatty acids to trigger a neuronal network to regulate VLDL-TG remain unknown. Here we demonstrate that infusion of oleic acid into the mediobasal hypothalamus (MBH) activates a MBH PKC-δ→KATP-channel signalling axis to suppress VLDL-TG secretion in rats. Both NMDA receptor-mediated transmissions in the dorsal vagal complex (DVC) and hepatic innervation are required for lowering VLDL-TG, illustrating a MBH-DVC-hepatic vagal neurocircuitry that mediates MBH fatty acid sensing. High-fat diet (HFD)-feeding elevates plasma TG and VLDL-TG secretion and abolishes MBH oleic acid sensing to lower VLDL-TG. Importantly, HFD-induced dysregulation is restored with direct activation of either MBH PKC-δ or KATP-channels via the hepatic vagus. Thus, targeting a fatty acid sensing-dependent hypothalamic–DVC neurocircuitry may have therapeutic potential to lower hepatic VLDL-TG and restore lipid homeostasis in obesity and diabetes.

Suggested Citation

  • Jessica T. Y. Yue & Mona A. Abraham & Mary P. LaPierre & Patricia I. Mighiu & Peter E. Light & Beatrice M. Filippi & Tony K. T. Lam, 2015. "A fatty acid-dependent hypothalamic–DVC neurocircuitry that regulates hepatic secretion of triglyceride-rich lipoproteins," Nature Communications, Nature, vol. 6(1), pages 1-11, May.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms6970
    DOI: 10.1038/ncomms6970
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