ArticlePloS one2019
Neurobehavioral dysfunction in non-alcoholic steatohepatitis is associated with hyperammonemia, gut dysbiosis, and metabolic and functional brain regional deficits.
Article in PloS one, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 2 of them syntheses that pooled it.
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Who cites it
35 citing papers in PubMed, 2 syntheses or guidelines pooled it, 61 citations in OpenAlex.
- Non-alcoholic Fatty Liver Disease: Also a Disease of the Brain? A Systematic Review of the Preclinical Evidence.Neurochemical research · 2024Pooled it
- Regulation of gut microbiome by ketogenic diet in neurodegenerative diseases: A molecular crosstalk.Frontiers in aging neuroscience · 2022Pooled it
- E-Selectin-Targeted Nanomicelles via Sialic Acid Conjugation for Anti-Inflammatory Efficacy and Alleviating the Progression of Metabolic-Associated Steatotic Liver Disease.Biomaterials research · 2026Article
- Article
- A narrative review about cognitive impairment in Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD): Another matter to face through a holistic approach.Journal of advanced research · 2025Review
- Effects of Metabolic Dysfunction-Associated Steatohepatitis in Alertness, Associative Learning, and Astrocyte Density.Brain and behavior · 2025Article
- Metagenomics Reveals Sex-Based Differences in Murine Fecal Microbiota Profiles Induced by Chronic Alcohol Consumption.International journal of molecular sciences · 2024Article
- Impacts of Different Perinatal Factors on Faecal Immune Compounds in Infants: Determination of Normal Values.International journal of molecular sciences · 2024Article
- The Effects of Rice Bran on Neuroinflammation and Gut Microbiota in Ovariectomized Mice Fed a Drink with Fructose.Nutrients · 2024Article
- The Metabolic Impact of Nonalcoholic Fatty Liver Disease on Cognitive Dysfunction: A Comprehensive Clinical and Pathophysiological Review.International journal of molecular sciences · 2024Review
- Double Trouble: How Microbiome Dysbiosis and Mitochondrial Dysfunction Drive Non-Alcoholic Fatty Liver Disease and Non-Alcoholic Steatohepatitis.Biomedicines · 2024Review
- Article
- Organic Selenium Alleviates Ammonia-Mediated Abnormal Autophagy by Regulating Inflammatory Pathways and the Keap1/Nrf2 Axis in the Hypothalamus of Finishing Pigs.Biological trace element research · 2023Article
- Mild Cognitive Impairment Is Associated with Enhanced Activation of Th17 Lymphocytes in Non-Alcoholic Fatty Liver Disease.International journal of molecular sciences · 2023Article
- Diabetes and fatty liver: Involvement of incretin and its benefit for fatty liver management.World journal of diabetes · 2023Review
- Curcumin-resveratrol nano-formulation counteracting hyperammonemia in rats.Metabolic brain disease · 2023Article
- Regulation of mild cognitive impairment associated with liver disease by humoral factors derived from the gastrointestinal tract and MRI research progress: a literature review.Frontiers in neuroscience · 2023Review
- Gut microbiota alterations are associated with functional outcomes in patients of acute ischemic stroke with non-alcoholic fatty liver disease.Frontiers in neuroscience · 2023Article
- Non-alcoholic fatty liver is associated with increased risk of irritable bowel syndrome: a prospective cohort study.BMC medicine · 2022Article
- Novel insights into non-alcoholic fatty liver disease and dementia: insulin resistance, hyperammonemia, gut dysbiosis, vascular impairment, and inflammation.Cell & bioscience · 2022Review
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Non-alcoholic steatohepatitis (NASH) is one of the most prevalent diseases worldwide. While it has been suggested to cause nervous impairment, its neurophysiological basis remains unknown. Therefore, the aim of this study is to unravel the effects of NASH, through the interrelationship of liver, gut microbiota, and nervous system, on the brain and human behavior. To this end, 40 Sprague-Dawley rats were divided into a control group that received normal chow and a NASH group that received a high-fat, high-cholesterol diet. Our results show that 14 weeks of the high-fat, high-cholesterol diet induced clinical conditions such as NASH, including steatosis and increased levels of ammonia. Rats in the NASH group also demonstrated evidence of gut dysbiosis and decreased levels of short-chain fatty acids in the gut. This may explain the deficits in cognitive ability observed in the NASH group, including their depressive-like behavior and short-term memory impairment characterized in part by deficits in social recognition and prefrontal cortex-dependent spatial working memory. We also reported the impact of this NASH-like condition on metabolic and functional processes. Brain tissue demonstrated lower levels of metabolic brain activity in the prefrontal cortex, thalamus, hippocampus, amygdala, and mammillary bodies, accompanied by a decrease in dopamine levels in the prefrontal cortex and cerebellum and a decrease in noradrenalin in the striatum. In this article, we emphasize the important role of ammonia and gut-derived bacterial toxins in liver-gut-brain neurodegeneration and discuss the metabolic and functional brain regional deficits and behavioral impairments in NASH.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.