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Table 2 Summarizes the common factors found to have a relevance in the pathogenesis of both NAFLD and psychiatric disorders

From: Non-alcoholic fatty liver disease (NAFLD) as a neglected metabolic companion of psychiatric disorders: common pathways and future approaches

Findings Normal function NAFLD Psychiatric disorders
Genetic PNPLA3 (adiponutrin) polymorphisms - Hydrolase activity on triglycerides and retinyl esters
- In pituitary: regulation of glucose and fatty acid homeostasis, appetite and energy expenditure
Linked to pathogenesis Bipolar disorder
- Unknown mechanism
- Probably linked to inflammation and oxidative stress
miR-34a - Hepatic lipogenesis & lipid secretion
- Neurodevelopment & synaptogenesis
NAFLD progression & heritability Bipolar disorder
- Elevated in diagnosed of BD
- Decreases in response to lithium
Mitochondria, inflammation and oxidative stress Altered mitochondrial metabolism - Protection against fatty acid accumulation
- Energy production
Excessive oxidative species are linked to hepatic inflammation, accumulation of fatty tissue and progression of NASH Linked to:
- Pathogenesis: neuroinflammation, dysregulation of brain energy generation & dysfunction in stress response mechanisms
- Progression & poorer outcomes
In several disorders:
- Bipolar disorder**
- Depression
- PTSD
- Psychosis & schizophrenia
- Autism
Microbiota Gut dysbiosis - Digestion of nutrients
- Production of vitamin K & B
- Maintenance of the intestinal mucosa
- Immune barrier effect
- Lipid accumulation in the liver
- Increased absorption of disaccharides
- Accelerated hepatic lipogenesis
- Inflammation and steatosis
ADHD, autism, depression, dementia
- Inflammatory dysregulation mediated by bacterial products
- Probiotics as suggested therapies
Psychological factors, lifestyle, exercise and diet Personality traits Enhancing adequate lifestyles - Weight gain and fatty tissue proliferation
- Dysregulation in immune response
Nonadaptive traits
- High neuroticism
- Low conscientiousness
Exercise Protective effects against inflammation Low activity linked to
- Weight gain and fat accumulation in liver
- Impaired glucose metabolism
- Upregulation of immune response, inflammation and fibrosis
Poorer mental health
- Low levels of activity linked to higher risk of depression
Impaired glucose metabolism and DM2 Regulating levels of exertion and fatigue during exercise - Weigh gain
- Accumulation of fatty tissue in liver
- Increased lipogenesis
- Increased ROS and lipid metabolism by-products
- Upregulation of inflammation
Unhealthy lifestyles
Link to higher risk of depression
Obesity Normal diet secures energy intake and essential nutrients NAFLD
- Fatty tissue proliferation
- Inflammation and oxidative stress
- Unhealthy lifestyles
- Medication adverse events
- Higher risk of depression