Liver sympathetic denervation reverses obesity‐induced hepatic steatosis

Abstract

Non-alcoholic fatty liver disease, characterized in part by elevated liver triglycerides (i.e. hepatic steatosis), is a growing health problem. r In this study, we found that hepatic steatosis is associated with robust hepatic sympathetic overactivity. r Removal of hepatic sympathetic nerves reduced obesity-induced hepatic steatosis. r Liver sympathetic innervation modulated hepatic lipid acquisition pathways during obesity.

Liver sympathetic nerve activity and steatosis

“…Whilst sympathetic nerve activity is important for regulating physiological processes in many tissues in healthy humans, the findings of Hurr et al . () are in line with suggestions that for some tissues (e.g. skeletal muscle and the kidneys), an abnormal increase in SNA can have a role in cardiometabolic disease pathogenesis (Guarino et al .…”

“…These mechanisms could now also be explored to develop the research of Hurr et al . (). The authors also acknowledged that direct recordings of afferent liver SNA were needed to support their results.…”

“…In a recent issue of The Journal of Physiology , Hurr et al . () provided evidence to support a role for increased liver sympathetic nerve activity (SNA) in the development of hepatic steatosis in obesity. The authors used a 10 week high‐fat diet (60% kcal from fat) to induce obesity and hepatic lipid accumulation in mice, which were compared to mice fed normal chow (with 5% kcal from fat).…”

“…Hurr et al . () also investigated potential mechanisms by which liver SNA may alter hepatic steatosis, using quantitative real time PCR to show that obese mice with hepatic steatosis exhibited an increased mRNA expression of proteins and transcription factors involved in hepatic lipid uptake and de novo lipogenesis. This upregulation of lipogenic genes was, however, mitigated by the inhibition of liver SNA.…”

“…In the work of Hurr et al . (), the increases in efferent nerve activity suggested that obesity‐associated alterations in liver SNA could be mostly attributable to central nervous system mechanisms, of which increased hypothalamic neuropeptide Y (NPY) expression is a likely candidate (Bruinstroop et al . ).…”