Sympathetic Overactivity to the Liver: A Possible Contributor to Hepatosteatosis in Diet‐Induced Obesity?

Abstract

Obesity is associated with hepatic pathologies, such as steatosis and fibrosis, but the involvement of the autonomic nervous system in these processes remains unclear. Given that elevations in sympathetic outflow play a role in other obesity‐induced diseases (e.g., hypertension), we tested the hypothesis that obesity is associated with hepatic sympathetic overactivity. Male C57Bl/6 mice were fed a high fat diet (HFD; 60% fat; n=5) or normal chow (5% fat, n=6) for 20 weeks and were then instrumented for direct anesthetized recordings of multifiber sympathetic nerve activity (SNA) to the liver. Hepatic SNA recordings revealed a near doubling of basal sympathetic outflow to the liver in HFD mice and this was evident when evaluated as a frequency (33±2 vs 63±5 spikes/s, normal chow vs HFD, p<0.05) or integrated voltage (0.28±0.02 vs 0.46±0.03 volts/s/min, normal chow vs HFD, p<0.05). Removal of afferent input, via cutting of the hepatic nerve distal to the recording electrode, indicated that elevated efferent sympathetic outflow was a large contributor to the increased basal liver SNA (efferent SNA: 0.23±0.02 vs 0.36±0.03 volts/s/min, normal chow vs HFD, p<0.05). These findings provide the first direct evidence of hepatic sympathetic overactivity in obesity and suggest that elevated liver SNA may play a role in obesity‐mediated hepatic disorders, including hepatosteatosis.HL63887, HL84207, K99HL166776