Impact of nonalcoholic fatty liver disease-related metabolic state on depression

Ntona, Smaragda; Papaefthymiou, Apostolis; Kountouras, Jannis; Gialamprinou, Dimitra; Kotronis, Georgios; Boziki, Marina; Polyzos, Stergios A.; Tzitiridou, Maria; Chatzopoulos, Dimitrios; Thavayogarajah, Tharshika; Gkolia, I; Ntonas, Georgios; Vardaka, Elisabeth; Doulberis, Michael

doi:10.1016/j.neuint.2023.105484

Cited by 11 publications

(9 citation statements)

References 143 publications

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“…MAFLD is characterized by gradual accumulation of lipids (>5% of hepatocytes in the absence of other pathogenic factors such as viral infections, drugs, and excessive alcohol intake), progressive liver inflammation, and fibrosis ( 6 ).…”

Section: Introductionmentioning

confidence: 99%

Time for micro-RNAs in steatotic liver disease: a case–control study

Stoica,

Apostol,

Diculescu

et al. 2024

Front. Endocrinol.

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One of the challenges of modern-day living is to resist the temptation of overfeeding and sedentariness and maintain a healthy body and mind. On a favorable genetic and epigenetic background, a high-fat diet combined with lack of physical exercise constitutes the foundation for severe metabolic disturbances including steatotic liver disease. In our case–control study, we had the aim of establishing the role of selected micro-RNAs—miR-122, miR-192, miR-33a, and miR-33b—as superior biomarkers for the diagnosis and prognosis of steatotic liver in a 36-patient cohort compared to 12 healthy controls. Initial results confirmed the decline in miR-122 expression as fatty liver is progressing. However, combinations of ΔmiRs, such as ΔmiR33a_192, ΔmiR33a_122, and ΔmiR33b_122, correlate with ultrasound steatosis grade (R2 = 0.78) while others such as ΔmiR33b_122 provide a high specificity and sensitivity in fatty liver disease with an area under the curve (AUC) of 0.85. Compared to classical biomarkers, micro-RNAs can be used for both diagnostic and prognostic purposes as their diminished expression in severe cases of steatosis is associated with higher risk of emerging hepatocellular carcinoma. Manipulating micro-RNAs through agomirs or antagomirs can be the answer to the yet unsolved problem of efficient therapy in MAFLD.

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Section: Introductionmentioning

confidence: 99%

Time for micro-RNAs in steatotic liver disease: a case–control study

Stoica,

Apostol,

Diculescu

et al. 2024

Front. Endocrinol.

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“…It is widely acknowledged that liver steatosis, characterized by the accumulation of fat in liver cells, often leads to a proinflammatory environment and activates microglial cells [ 67 ]. Moreover, it has been suggested that liver steatosis can also trigger a systemic hyperinflammatory state, which can result in damage to the PFC—a phenomenon frequently observed in depression [ 68 ]. Our results showed that the morphology of liver cells was significantly altered in CUMS-induced depression in rats and that the increase in the expression of CD68, upregulation of P2X7R/NLRP3/IL-1β expression, and increase in the release of proinflammatory cytokine IL-1β were all improved by EA as well as the intraperitoneal injection of BBG.…”

Section: Discussionmentioning

confidence: 99%

Electroacupuncture Alleviates Depressive-like Behavior by Modulating the Expression of P2X7/NLRP3/IL-1β of Prefrontal Cortex and Liver in Rats Exposed to Chronic Unpredictable Mild Stress

et al. 2023

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Depression is a complex clinical disorder associated with poor outcomes. Electroacupuncture (EA) has been demonstrated to have an important role in both clinical and pre-clinical depression investigations. Evidence has suggested that the P2X7 receptor (P2X7R), NLRP3, and IL-1β play an important role in depressive disorder. Our study is aimed at exploring the role of EA in alleviating depression-like behaviors in rats. We therefore investigated the effects of EA on the prefrontal cortex and liver of rats subjected to chronic unpredictable mild stress (CUMS) through behavior tests, transmission electron microscopy, Nissl staining, HE staining, immunohistochemistry and Western blotting. Five weeks after exposure to CUMS, Sprague-Dawley (SD) rats showed depression-like behavior. Three weeks after treatment with brilliant blue G (BBG) or EA, depressive symptoms were significantly improved. Liver cells and microglia showed regular morphology and orderly arrangement in the BBG and EA groups compared with the CUMS group. Here we show that EA downregulated P2X7R/NLRP3/IL-1β expression and relieved depression-like behavior. In summary, our findings demonstrated the efficacy of EA in alleviating depression-like behaviors induced by CUMS in rats. This suggests that EA may serve as an adjunctive therapy in clinical practice, and that P2X7R may be a promising target for EA intervention on the liver–brain axis in treatment of depression.

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“…Compared to the non-NAFLD population, the risk of developing depression is 13% higher in individuals with NAFLD, and the risk of NAFLD is signi cantly increased by 46% in people with depression [16]. NAFLD and depression share some common risk factors such as obesity, metabolic syndrome, and T2D [17]. Adiposity and dysregulation of adipose tissue lipid metabolism in NAFLD are thought to be involved in the pathogenesis of depression, suggesting an important role for obesity and adipose tissue function in the liver-brain axis in NAFLD [18, 19.…”

Section: Introductionmentioning

confidence: 99%

Association between Weight-Adjusted Waist Index and Depression in NAFLD: The Modulating Roles of Sex and BMI

Zhang,

Wang,

Xie

et al. 2024

Preprint

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Background The Weight-Adjusted Waist Index (WWI) is a novel indicator of obesity that accurately reflects body composition. However, the association between WWI and depression in patients with non-alcoholic fatty liver disease (NAFLD) remains unclear. This study aims to explore this relationship through a nationally representative cross-sectional analysis. Methods This study included adult participants diagnosed with NAFLD from NHANES 2017–2020. WWI was calculated as the waist circumference (cm) divided by the square root of body weight (kg). NAFLD diagnosis relied on vibration-controlled transient elastography (VCTE) with a controlled attenuation parameter (CAP) exceeding 248 dB/m to indicate hepatic steatosis. Depression was assessed using the Patient Health Questionnaire-9 (PHQ-9), with scores ≥ 10 indicating the presence of major depression. Results After adjusting for all covariates, a significant positive association was found between WWI and depression in NAFLD (OR = 1.725, 95% CI: 1.442–2.063, p < 0.00001), with a dose-response relationship indicated by restricted cubic spline analysis. The association was stronger in men and lean NAFLD patients. Adjusting further for BMI did not alter these findings (OR = 1.643, 95% CI: 1.357–1.989, p < 0.00001). BMI's association with depression was negated after adjusting for WWI. Conclusions WWI had a positive association with depression in NAFLD, independent of BMI. This association was more pronounced in men and lean NAFLD. These findings suggest that WWI may be a novel predictor of depression in NAFLD and potentially valuable in depression prevention.

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Impact of nonalcoholic fatty liver disease-related metabolic state on depression

Cited by 11 publications

References 143 publications

Time for micro-RNAs in steatotic liver disease: a case–control study

Time for micro-RNAs in steatotic liver disease: a case–control study

Electroacupuncture Alleviates Depressive-like Behavior by Modulating the Expression of P2X7/NLRP3/IL-1β of Prefrontal Cortex and Liver in Rats Exposed to Chronic Unpredictable Mild Stress

Association between Weight-Adjusted Waist Index and Depression in NAFLD: The Modulating Roles of Sex and BMI

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