Endocrine Abstracts

The brain influences liver metabolism through many neuroendocrine and autonomic mechanisms that have evolved to protect the organism against starvation and hypoglycemia by maintaining energy and glucose homeostasis. Unfortunately, these sophisticated homeostatic processes can be impaired in metabolic diseases such as obesity, type 2 diabetes and metabolic associated steatotic liver disease (MASLD). However, the precise mechanisms by which the brain regulates hepatic metabolism, how autonomic dysfunctions can alter brain-liver communication, and whether alterations in the autonomic outflow to the liver contribute to disease progression, remain to be defined. Based on recent tissue clearing studies showing that neural innervations within the liver are of sympathetic nature, we hypothesized that adrenergic receptors expressed by hepatocytes directly mediate the autonomic control of liver metabolism. Our data indicate that liver adrenoceptors play a protective role in the progression of metabolic diseases. We found sex-dependent mechanisms by which the sympathetic nervous system regulates energy and glucose homeostasis through the liver. We believe that a better understanding of the receptors and pathways involved in the sympathetic outflow of the liver will help.