Journal article
Liver sympathetic denervation reverses obesity‐induced hepatic steatosis
The Journal of physiology, Vol.597(17), pp.4565-4580
09/01/2019
DOI: 10.1113/JP277994
PMCID: PMC6716997
PMID: 31278754
Abstract
Key points
Non‐alcoholic fatty liver disease, characterized in part by elevated liver triglycerides (i.e. hepatic steatosis), is a growing health problem.
In this study, we found that hepatic steatosis is associated with robust hepatic sympathetic overactivity.
Removal of hepatic sympathetic nerves reduced obesity‐induced hepatic steatosis.
Liver sympathetic innervation modulated hepatic lipid acquisition pathways during obesity.
Non‐alcoholic fatty liver disease (NAFLD) affects 1 in 3 Americans and is a significant risk factor for type II diabetes mellitus, insulin resistance and hepatic carcinoma. Characterized in part by excessive hepatic triglyceride accumulation (i.e. hepatic steatosis), the incidence of NAFLD is increasing – in line with the growing obesity epidemic. The role of the autonomic nervous system in NAFLD remains unclear. Here, we show that chronic hepatic sympathetic overactivity mediates hepatic steatosis. Direct multiunit recordings of hepatic sympathetic nerve activity were obtained in high fat diet and normal chow fed male C57BL/6J mice. To reduce hepatic sympathetic nerve activity we utilized two approaches including pharmacological ablation of the sympathetic nerves and phenol‐based hepatic sympathetic nerve denervation. Diet‐induced NAFLD was associated with a nearly doubled firing rate of the hepatic sympathetic nerves, which was largely due to an increase in efferent nerve traffic. Furthermore, established high fat diet‐induced hepatic steatosis was effectively reduced with pharmacological or phenol‐based removal of the hepatic sympathetic nerves, independent of changes in body weight, caloric intake or adiposity. Ablation of liver sympathetic nerves was also associated with improvements in liver triglyceride accumulation pathways including free fatty acid uptake and de novo lipogenesis. These findings highlight an unrecognized pathogenic link between liver sympathetic outflow and hepatic steatosis and suggest that manipulation of the liver sympathetic nerves may represent a novel therapeutic strategy for NAFLD.
Key points
Non‐alcoholic fatty liver disease, characterized in part by elevated liver triglycerides (i.e. hepatic steatosis), is a growing health problem.
In this study, we found that hepatic steatosis is associated with robust hepatic sympathetic overactivity.
Removal of hepatic sympathetic nerves reduced obesity‐induced hepatic steatosis.
Liver sympathetic innervation modulated hepatic lipid acquisition pathways during obesity.
Details
- Title: Subtitle
- Liver sympathetic denervation reverses obesity‐induced hepatic steatosis
- Creators
- Chansol Hurr - Chonbuk National UniversityHayk Simonyan - The George Washington UniversityDonald A Morgan - University of IowaKamal Rahmouni - University of IowaColin N Young - The George Washington University
- Resource Type
- Journal article
- Publication Details
- The Journal of physiology, Vol.597(17), pp.4565-4580
- DOI
- 10.1113/JP277994
- PMID
- 31278754
- PMCID
- PMC6716997
- ISSN
- 0022-3751
- eISSN
- 1469-7793
- Number of pages
- 16
- Grant note
- National Heart, Lung, and Blood Institute (R00HL116776; P01HL084207) National Institute of Diabetes and Digestive and Kidney Diseases (R01DK117007)
- Language
- English
- Date published
- 09/01/2019
- Academic Unit
- Iowa Neuroscience Institute; Fraternal Order of Eagles Diabetes Research Center; Neuroscience and Pharmacology; Internal Medicine
- Record Identifier
- 9984070443702771
Metrics
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