Non-alcoholic fatty liver disease (NAFLD) and mental illness: Mechanisms linking mood, metabolism and medicines

Abstract

Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the world and one of the leading indications for liver transplantation. It is one of the many manifestations of insulin resistance and metabolic syndrome as well as an independent risk factor for cardiovascular disease. There is growing evidence linking the incidence of NAFLD with psychiatric illnesses such as schizophrenia, bipolar disorder and depression mechanistically via genetic, metabolic, inflammatory and environmental factors including smoking and psychiatric medications. Indeed, patients prescribed antipsychotic medications, regardless of diagnosis, have higher incidence of NAFLD than population norms. The mechanistic pharmacology of antipsychotic-associated NAFLD is beginning to emerge. In this review, we aim to discuss the pathophysiology of NAFLD including its risk factors, insulin resistance and systemic inflammation as well as its intersection with psychiatric illnesses.

Liver-innervating vagal sensory neurons are indispensable for the development of hepatic steatosis and anxiety-like behavior in diet-induced obese mice

“…The animal behavior tests we conducted showed that the experimental mice were more inclined to explore novel and unprotected areas, suggesting that they were less anxious and more motivated than the control mice. Although it appears that impaired hepatic lipid metabolism significantly affects psychiatric disorders [13][14][15] , the underlying mechanisms remains poorly understood. Our results suggests that liver-innervating vagal sensory neurons may play an important role in developing psychiatric disorders in patients with obesity and NAFLD.…”

“…We used AAVrg-Cre (Addgene 55636-AAVrg, titer; 2.2 x10 13 pfu/ml), AAVrg-FLEX-GFP (Addgene 51502-AAVrg, titer; 2.3 x10 13 pfu/ml), AAVrg-FLEX-jGCamp7s (Addgene 104491, titer; 2.5 x10 13 pfu/ml). Avil CreERT2 mice received a total volume of 20 ul of viral injection into the medial and left lobes of the livers.…”

“…Although the brain is the most energy-demanding organ in the body, it remains relatively unknown whether hepatic metabolism can influence brain function. In fact, individuals with nonalcoholic fatty liver disease (NAFLD) have a higher risk of psychiatric disorders including anxiety, depression, bipolar disorder, schizophrenia, and dementia [13][14][15] , suggesting that impaired hepatic lipid metabolism may be closely associated with mental illness. As liver-derived interoceptive signaling molecules can reach higher brain centers via hepatic vagal sensory neurons and humoral pathways, it is reasonable to assume that disrupted interoceptive signaling caused by NAFLD may result in psychiatric illness.…”

Global research on portal vein thrombosis and liver transplantation: A bibliometric and visualized study

“…[37] The synergistic effect of obesity and insulin resistance leads to chronic inflammation and impaired fibrinolysis, putting the body in a thrombotic state and becoming an independent risk factor for portal vein thrombosis in liver transplant patients. [38] Many countries, led by the United States, mainly treat metabolic diseases such as obesity and diabetes by improving patients lifestyles, drugs, surgery, or endoscopy to prevent PVT in NAFLD transplant patients. [37] A high-protein, low-calorie diet, and long-term moderate-intensity physical exercise in liver transplant patients can reduce the body quality of patients without compromising the protein storage in liver transplant patients.…”

NPC1L1 Plays a Novel Role in Nonalcoholic Fatty Liver Disease

“…With the improvement of living standards and the change of diet structure and lifestyle, the incidence of nonalcoholic steatohepatitis (NASH) caused by obesity, hyperlipidemia, and diabetes is gradually increasing. , Some NASH patients even develop liver fibrosis and cirrhosis, which can lead to serious consequences. NASH is a key stage in the disease spectrum of nonalcoholic fatty liver disease (NAFLD), which is the necessary process for the development of simple fatty liver into fatty liver fibrosis and cirrhosis . At present, the pathological mechanism of NASH has not been clarified, and there is a lack of specific clinical treatment methods.…”