Hepatokines, bile acids and ketone bodies are novel Hormones regulating energy homeostasis

Current views show that an impaired balance partly explains the fat accumulation leading to obesity. Fetal malnutrition and early exposure to endocrine-disrupting compounds also contribute to obesity and impaired insulin secretion and/or sensitivity. The liver plays a major role in systemic glucose homeostasis through hepatokines secreted by hepatocytes. Hepatokines influence metabolism through autocrine, paracrine, and endocrine signaling and mediate the crosstalk between the liver, non-hepatic target tissues, and the brain. The liver also synthetizes bile acids (BAs) from cholesterol and secretes them into the bile. After food consumption, BAs mediate the digestion and absorption of fat-soluble vitamins and lipids in the duodenum. In recent studies, BAs act not simply as fat emulsifiers but represent endocrine molecules regulating key metabolic pathways. The liver is also the main site of the production of ketone bodies (KBs). In prolonged fasting, the brain utilizes KBs as an alternative to CHO. In the last few years, the ketogenic diet (KD) became a promising dietary intervention. Studies on subjects undergoing KD show that KBs are important mediators of inflammation and oxidative stress. The present review will focus on the role played by hepatokines, BAs, and KBs in obesity, and diabetes prevention and management and analyze the positive effects of BAs, KD, and hepatokine receptor analogs, which might justify their use as new therapeutic approaches for metabolic and aging-related diseases.

Automated summary

Current perspectives suggest that an impaired balance, fetal malnutrition, and exposure to endocrine-disrupting compounds contribute to obesity and impaired insulin function. Additionally, the liver plays a crucial role in maintaining glucose balance through hepatokines, bile acids, and ketone bodies. Recent studies have revealed that bile acids and ketone bodies act as endocrine molecules that regulate key metabolic pathways and mediate inflammation and oxidative stress. This review focuses on the role of hepatokines, bile acids, and ketone bodies in obesity, diabetes prevention and management, and explores their potential as therapeutic approaches for metabolic and aging-related diseases.