Hypothalamus-liver talks: whispers in the language of metabolism

Abstract

Closely associated with the exponential increase of obesity and sedentary life, liver-related disorders are a major global health concern. Recent data suggest that the global prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) among adults is of 32% and 5.1% for alcohol-related liver disease, with hepatic disorders contributing to 4% of global mortality, accounting for approximately 2 million deaths annually. Over the past two decades, the hypothalamus has emerged as a central hub in regulating whole body metabolic and energy homeostasis. Nevertheless, the interactome between the hypothalamus and the liver in the progression of liver metabolic dysfunctions, as well as its potential as a therapeutic target, remains poorly understood. In this review, we provide a comprehensive overview of the current knowledge regarding the hypothalamus-liver crosstalk, with a particular emphasis on the mechanisms underlying it. We explore how signals transmitted by different hormones can modulate these interactions, shedding light on their functional implications for hepatic regulation and systemic homeostasis through central signals.