Depressive symptoms in non-alcoholic fatty liver disease are identified by perturbed lipid and lipoprotein metabolism

Radford-Smith, Daniel E.; Patel, Preya; Irvine, Katharine M.; Russell, Anthony; Siskind, Dan; Anthony, D C; Powell, Elizabeth E.; Probert, Fay

doi:10.1371/journal.pone.0261555

Cited by 6 publications

(3 citation statements)

References 31 publications

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“…When these brain regions are DA-deficient, slow, uncoordinated movements and impaired cognition were reported, akin to the OFT and NORT results in WD-fed mice. These results further support that low brain DA concentrations are associated with motor depression and cognitive dysfunction in MASH [55][56][57][58].…”

Section: Discussionsupporting

confidence: 77%

Cognitive Functions, Neurotransmitter Alterations, and Hippocampal Microstructural Changes in Mice Caused by Feeding on Western Diet

Custodio,

Hobloss,

Myllys

et al. 2023

Cells

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Metabolic Dysfunction Associated Steatotic Liver Disease (MASLD) is the most common chronic liver disease in Western countries. It is becoming increasingly evident that peripheral organ-centered inflammatory diseases, including liver diseases, are linked with brain dysfunctions. Therefore, this study aims to unravel the effect of MASLD on brain histology, cognitive functions, and neurotransmitters. For this purpose, mice fed for 48 weeks on standard (SD) or Western diet (WD) were evaluated by behavioral tests, followed by sacrifice and analysis of the liver-brain axis including histopathology, immunohistochemistry, and biochemical analyses. Histological analysis of the liver showed features of Metabolic Dysfunction-Associated Steatohepatitis (MASH) in the WD-fed mice including lipid droplet accumulation, inflammation, and fibrosis. This was accompanied by an elevation of transaminase and alkaline phosphatase activities, increase in inflammatory cytokine and bile acid concentrations, as well as altered amino acid concentrations in the blood. Interestingly, compromised blood capillary morphology coupled with astrogliosis and microgliosis were observed in brain hippocampus of the WD mice, indicating neuroinflammation or a disrupted neurovascular unit. Moreover, attention was impaired in WD-fed mice along with the observations of impaired motor activity and balance, enhanced anxiety, and stereotyped head-twitch response (HTR) behaviors. Analysis of neurotransmitters and modulators including dopamine, serotonin, GABA, glutamate, and acetylcholine showed region-specific dysregulation in the brain of the WD-fed mice. In conclusion, the induction of MASH in mice is accompanied by the alteration of cellular morphology and neurotransmitter expression in the brain, associated with compromised cognitive functions.

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Section: Discussionsupporting

confidence: 77%

Cognitive Functions, Neurotransmitter Alterations, and Hippocampal Microstructural Changes in Mice Caused by Feeding on Western Diet

Custodio,

Hobloss,

Myllys

et al. 2023

Cells

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“…At an individual level, they can reduce the quality of life of those affected. Substantial epidemiological evidence exists for a bidirectional relationship between depression and obesity [147][148][149][150]. A meta-analysis of longitudinal studies found that obese individuals had a 55% increased risk of developing depression over time, while depressed persons were 58% more likely to become obese [147].…”

Section: Depression and Obesity: A Bidirectional Relationshipmentioning

confidence: 99%

Prebiotic and Probiotic Modulation of the Microbiota–Gut–Brain Axis in Depression

Radford-Smith

Anthony

2023

Nutrients

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Emerging evidence demonstrates that alterations to the gut microbiota can affect mood, suggesting that the microbiota–gut–brain (MGB) axis contributes to the pathogenesis of depression. Many of these pathways overlap with the way in which the gut microbiota are thought to contribute to metabolic disease progression and obesity. In rodents, prebiotics and probiotics have been shown to modulate the composition and function of the gut microbiota. Together with germ-free rodent models, probiotics have provided compelling evidence for a causal relationship between microbes, microbial metabolites, and altered neurochemical signalling and inflammatory pathways in the brain. In humans, probiotic supplementation has demonstrated modest antidepressant effects in individuals with depressive symptoms, though more studies in clinically relevant populations are needed. This review critically discusses the role of the MGB axis in depression pathophysiology, integrating preclinical and clinical evidence, as well as the putative routes of communication between the microbiota–gut interface and the brain. A critical overview of the current approaches to investigating microbiome changes in depression is provided. To effectively translate preclinical breakthroughs in MGB axis research into novel therapies, rigorous placebo-controlled trials alongside a mechanistic and biochemical understanding of prebiotic and probiotic action are required from future research.

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“…Overall, there is increasing evidence of a bidirectional relationship between NAFLD and such mental health conditions, with reports suggesting that NAFLD may increase the risk of depression and anxiety, and that depressed individuals might be more likely to develop NAFLD, independently of other comorbidities [54]. However, it is noted that there may be other underlying factors in relation to these associations, including links between depression and/or anxiety and unhealthy lifestyle behaviours [10].…”

Section: Nafld and Mental Healthmentioning

confidence: 99%

Support Needs and Coping Strategies in Non-Alcoholic Fatty Liver Disease (NAFLD): A Multidisciplinary Approach to Potential Unmet Challenges beyond Pharmacological Treatment

Shea

Lionis

Atkinson

et al. 2022

Livers

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Non-alcoholic fatty liver disease (NAFLD) is the most frequently occurring chronic liver disease, affecting approximately 25–30% of the adult general population worldwide. NAFLD reflects excess hepatic accumulation of fat in the absence of increased alcohol intake, and, due to its close association with obesity, is frequently referred to as the ‘hepatic manifestation’ of metabolic syndrome. Indeed, a high percentage of individuals with NAFLD present with a combination of the cardio-metabolic comorbidities that are associated with the metabolic syndrome. In addition to its well-established link with the metabolic syndrome and increased risk for cardiovascular disease, NAFLD has also been associated with certain mental health issues (e.g., depression and stress). Although this link is now being increasingly recognized, there are still unmet needs regarding the holistic management of patients with NAFLD, which could further contribute to feelings of social isolation and loneliness. The latter conditions are also increasingly reported to pose a substantial risk to overall health and quality of life. To date, there is limited research that has explored these issues among patients with NAFLD, despite existing data which indicate that perceived loneliness and isolation may pose an additional health risk. Notably, many features associated with NAFLD have been related to these concepts, such as perceived stigma, fatigue, stress, and confusion regarding this diagnosis. As such, this review aimed to assess such potential problems faced by patients with NAFLD, and to explore the possibility of unmet support needs which could lead to perceived social isolation. Moreover, the importance of a compassionate approach towards such patients is discussed, together with potential coping strategies. Future research directions and the need for a multidisciplinary approach are also highlighted.

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Depressive symptoms in non-alcoholic fatty liver disease are identified by perturbed lipid and lipoprotein metabolism

Cited by 6 publications

References 31 publications

Cognitive Functions, Neurotransmitter Alterations, and Hippocampal Microstructural Changes in Mice Caused by Feeding on Western Diet

Cognitive Functions, Neurotransmitter Alterations, and Hippocampal Microstructural Changes in Mice Caused by Feeding on Western Diet

Prebiotic and Probiotic Modulation of the Microbiota–Gut–Brain Axis in Depression

Support Needs and Coping Strategies in Non-Alcoholic Fatty Liver Disease (NAFLD): A Multidisciplinary Approach to Potential Unmet Challenges beyond Pharmacological Treatment

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