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

Nat Commun. 2015 Jan 12;6:5970. doi: 10.1038/ncomms6970.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / metabolism
  • Animals
  • Apolipoproteins B / metabolism
  • Brain / metabolism
  • Fatty Acids / chemistry*
  • Green Fluorescent Proteins / metabolism
  • Homeostasis
  • Hypothalamus / metabolism*
  • Lipoproteins / metabolism*
  • Lipoproteins, VLDL
  • Liver / innervation
  • Liver / metabolism*
  • Male
  • Neurons / physiology
  • Oleic Acid / chemistry
  • Potassium Channels / metabolism
  • Protein Kinase C / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Triglycerides / metabolism*
  • Vagus Nerve / physiology

Substances

  • Apolipoproteins B
  • Fatty Acids
  • Lipoproteins
  • Lipoproteins, VLDL
  • Potassium Channels
  • Triglycerides
  • lipoprotein triglyceride
  • very low density lipoprotein triglyceride
  • Green Fluorescent Proteins
  • Oleic Acid
  • Protein Kinase C