Linking Nonalcoholic Fatty Liver Disease and Brain Disease: Focusing on Bile Acid Signaling

Abstract

A metabolic illness known as non-alcoholic fatty liver disease (NAFLD), affects more than one-quarter of the world’s population. Bile acids (BAs), as detergents involved in lipid digestion, show an abnormal metabolism in patients with NAFLD. However, BAs can affect other organs as well, such as the brain, where it has a neuroprotective effect. According to a series of studies, brain disorders may be extrahepatic manifestations of NAFLD, such as depression, changes to the cerebrovascular system, and worsening cognitive ability. Consequently, we propose that NAFLD affects the development of brain disease, through the bile acid signaling pathway. Through direct or indirect channels, BAs can send messages to the brain. Some BAs may operate directly on the central Farnesoid X receptor (FXR) and the G protein bile acid-activated receptor 1 (GPBAR1) by overcoming the blood–brain barrier (BBB). Furthermore, glucagon-like peptide-1 (GLP-1) and the fibroblast growth factor (FGF) 19 are released from the intestine FXR and GPBAR1 receptors, upon activation, both of which send signals to the brain. Inflammatory, systemic metabolic disorders in the liver and brain are regulated by the bile acid-activated receptors FXR and GPBAR1, which are potential therapeutic targets. From a bile acid viewpoint, we examine the bile acid signaling changes in NAFLD and brain disease. We also recommend the development of dual GPBAR1/FXR ligands to reduce side effects and manage NAFLD and brain disease efficiently.

Steatotic liver disease is the most important somatic determinant of quality of life in patients with obesity: A cross‐sectional study

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“…In the analysis of each SIP statement, it is evident that physical discomfort, reduced activity levels, especially in the sphere of sexuality, and challenges related to attention are the prevailing issues that significantly impact the daily lives of our study participants—and more so in patients with MASH. The reason for these problems is likely multifactorial, but others have proposed that a mild hepatic encephalopathy or a ‘new’ composite metabolic encephalopathy might exist in metabolically dysfunctional patients with or without obesity 31–35 . If present, this could adversely impact QOL, particularly attention span and low activity level, which are well‐known problems in HE.…”

Intermittent Fasting on Neurologic Diseases: Potential Role of Gut Microbiota

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Bile acid signalling and its role in anxiety disorders

“…Earlier studies have also described that bile acids transmit signals to the brain through both direct or indirect pathways and participate in the development of brain diseases, thereby implying a correlation between bile acids and mental illnesses. Elevated serum bile acids have been proven to increase BBB permeability and transmit signals to the central nervous system via FXR, TGR5, etc., eventually elevating the risk of mental disorders ( 9 ).However, the underlying mechanisms by which bile acid signals affect the occurrence of anxiety behavior have not been fully elucidated ( 10 ). The article is divided into two main sections.…”