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

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.

• Authors: Jessica T Y Yue, Mona A Abraham, Mary P LaPierre, Patricia I Mighiu, Peter E Light, Beatrice M Filippi, Tony K T Lam
• Journal: Nature communications (Nat Commun) Vol. 6 Pg. 5970 (Jan 12 2015) ISSN: 2041-1723 [Electronic] England
• PMID: 25580573 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 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

Topics

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