Effects of Sympathetic Denervation in Metabolism Regulation: A Novel Approach for the Treatment of MASLD?

Abstract

Although metabolic dysfunction-associated steatotic liver disease (MASLD), previously termed nonalcoholic fatty liver disease, has become the most common chronic liver disorder, its complex pathophysiology has not been fully elucidated up to date. A correlation between elevated sympathetic activation and MASLD has been highlighted in recent preclinical and clinical studies. Furthermore, increased sympathetic activity has been associated with the main mechanisms involved in MASLD, such as lipid accumulation in the liver, insulin resistance, and metabolic dysregulation, while it has been also correlated with the progression of MASLD, leading to liver fibrosis. Preclinical studies demonstrated that therapies which ameliorate the activation of the sympathetic nervous system, such as renal and liver sympathetic denervation, reduce hepatic insulin resistance, decrease hepatic glucose production, and reverse hepatic steatosis in high-fat-diet models. However, data from clinical trials regarding the effect of renal denervation on metabolic parameters are conflicting, since several trials reported a favorable effect, while other trials stated no significant difference, with the profound limitation of the lack of originally designed denervation trials in this setting. Thus, a thorough review of the role of the sympathetic nervous system in the pathophysiology of MASLD, as well as the results of recent sympathetic denervation studies and trials regarding metabolic regulation and MASLD treatment would be of great importance.