Systemic chemical sympathectomy does not alter the long-term course of disease in a murine model of non-alcoholic steatohepatitis

The effect of sympathetic innervation on the process of liver steatosis and development of non-alcoholic steatohepatitis is poorly understood. Our aim was to investigate the effect of systemic chemical sympathectomy (SE) by utilizing 6-hydroxydopamine (6-OHDA) on the course of a Paigen-diet induced steatohepatitis in mice. Steatosis was assessed semiquantitatively by histology, intrahepatic measurement of triglycerides, cholesterol and free fatty acids. Inflammation and fibrosis were graded on histology and key modulators (TNF, collagen alpha1) determined by Taqman-PCR. Results: At 12 and 24 weeks, Paigen-diet induced hepatic steatosis, increased serum transaminases and increased intrahepatic expression of TNF and collagen-alpha-1. At 12 weeks, prior SE significantly increased hepatic steatosis being mainly due to an additional increase in intrahepatic accumulation of cholesterol and free fatty acids. However, Paigen-diet induced TNF-expression as well as collagen-alpha1-expression were attenuated by prior SE without significant changes in serum transaminases or inflammation on liver histology. At week 24, no more significant difference in measures of steatosis, inflammation or fibrogenesis were detectable between paigen-fed animals with and without prior SE. Conclusion: In the early course of murine Paigen-diet induced steatohepatitis, destruction of sympathetic nerve fibres aggravates hepatic steatosis but ameliorates pro-inflammatory and -fibrogenic signaling. In contrast, the long-term course of steatohepatitis is not significantly altered by systemic sympathectomy indicating different roles of sympathetic neurotransmitters in different stages of disease.

NASH - liver fibrogenesis - sympathetic nervous system