The hepatoprotective effects of n3-polyunsaturated fatty acids against non-alcoholic fatty liver disease in diabetic rats through the FOXO1/PPARα/GABARAPL1 signalling pathway

Ramadan, Nehal M.; Elmasry, Khaled; Elsayed, Hassan; El-Mesery, Ahmed; Eraky, Salma M.

doi:10.1016/j.lfs.2022.121145

Cited by 9 publications

(6 citation statements)

References 66 publications

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“…FoxO1 is a key transcription factor majorly involved in GABARAPL1 transcription and insulin signaling 23 24 . To further determine whether insulin suppresses GABARAPL1 transcription by blocking binding of FoxO1 to IREs of GABARAPL1 gene promoter, we designed 5 IRE site-specific mutations in GABARAPL1 gene promoter as indicated in Fig.…”

Section: Resultsmentioning

confidence: 99%

Insulin Inhibits Autophagy by Inhibiting the Binding of FoXO1 to the Promoter Region of GABARAPL1

et al. 2023

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Hyperinsulinemia and insulin resistance in T2D has a potent suppressive effect on hepatic autophagy, however, the underlying mechanisms remain unclear. To explore the effect of insulin on hepatic autophagy and it’s possible signaling pathways, HL-7702 cells were treated by insulin with or without insulin signaling inhibitors. The interaction between insulin and the promoter region of GABARAPL1 was assessed through luciferase assay and EMSA. There were significant dose-dependent decreases in the number of intracellular autophagosomes and the protein levels of GABARAPL1 and beclin1 in insulin-treated HL-7702 cells. Insulin signaling inhibitors reversed the inhibitory effect of insulin on rapamycin-induced autophagy and autophagy-related gene upregulation. Insulin block the binding of FoxO1 to putative insulin response elements in GABARAPL1 gene promoter, leading to the repressed transcription of GABARAPL1 gene and the suppression of hepatic autophagy. Our study identified GABARAPL1 as a novel target of insulin in suppressing hepatic autophagy.

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Section: Resultsmentioning

confidence: 99%

Insulin Inhibits Autophagy by Inhibiting the Binding of FoXO1 to the Promoter Region of GABARAPL1

et al. 2023

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“…Several studies have investigated the relationship between pathogenesis and miRNAs in MASH/MASLD [ 72 ]. MiRNAs regulate various signaling pathways [ 73 ] such as PI3K-AKT, mTOR, FOXO, AMPK, NF-kappa B, or TNFα, among others, which are linked to MASLD development [ 74 , 75 , 76 ]. These pathways intersect with factors like lipid accumulation, IR, oxidative stress, HSC activation, and inflammatory responses, thereby contributing to MASLD pathogenesis [ 77 ].…”

Section: Discussionmentioning

confidence: 99%

Multipanel Approach including miRNAs, Inflammatory Markers, and Depressive Symptoms for Metabolic Dysfunction-Associated Steatotic Liver Disease Diagnosis during 2-Year Nutritional Intervention

Tobaruela-Resola,

Riezu-Boj,

Milagro

et al. 2024

Nutrients

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Metabolic dysfunction-associated steatotic liver disease (MASLD), with a prevalence of 30% of adults globally, is considered a multifactorial disease. There is a lack of effective non-invasive methods for accurate diagnosis and monitoring. Therefore, this study aimed to explore associations between changes in circulating miRNA levels, inflammatory markers, and depressive symptoms with hepatic variables in MASLD subjects and their combined potential to predict the disease after following a dietary intervention. Biochemical markers, body composition, circulating miRNAs and hepatic and psychological status of 55 subjects with MASLD with obesity and overweight from the FLiO study were evaluated by undergoing a 6-, 12- and 24-month nutritional intervention. The highest accuracy values of combined panels to predict the disease were identified after 24 months. A combination panel that included changes in liver stiffness, high-density lipoprotein cholesterol (HDL-c), body mass index (BMI), depressive symptoms, and triglycerides (TG) yielded an AUC of 0.90. Another panel that included changes in hepatic fat content, total cholesterol (TC), miR15b-3p, TG, and depressive symptoms revealed an AUC of 0.89. These findings identify non-invasive biomarker panels including circulating miRNAs, inflammatory markers, depressive symptoms and other metabolic variables for predicting MASLD presence and emphasize the importance of precision nutrition in MASLD management and the sustained adherence to healthy lifestyle patterns.

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“…GABARAPL1 is a well-known autophagy related gene, but it also in uences the sensitivity of cancer stem-like cells to ferroptosis [24]. GABARAPL1 is involved in the hepatoprotective effect of n3-polyunsaturated fatty acids on non-alcoholic fatty liver in diabetic rats [25]. ACSL1 can mediate the ferroptosis caused by conjugated linolenic acids [26].…”

Section: Discussionmentioning

confidence: 99%

Construct a prognostic model based on fatty acid metabolism/ferroptosis-related genes and reveal the immune heterogeneity and somatic mutation specificity of rectal adenocarcinoma in different groups

Wang,

Chen,

et al. 2023

Preprint

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Background: The prognosis of late stage rectal adenocarcinoma (READ) patients is poor and the recurrence rate is high. The aim of this research is to explore the prognostic value and underlying molecular mechanism of genes related to fatty acid metabolism/ferroptosis in READ. Methods: All data and clinical information were obtained by accessing public databases. A risk model was constructed based on fatty acid metabolism/ferroptosis-related genes by LASSO algorithm and Cox regression analysis. Then, relationship between the risk score and various clinical characteristics was analyzed. Subsequently, a nomogram was constructed to assess survival. The characteristics of immune microenvironment and somatic mutations in different groups were also investigated. Results: A risk score constructed based on 6 fatty acid metabolism/ferroptosis-related genes was found to be independent prognostic factors of READ and was also associated with disease progression. According to the Kaplan-Meier analysis, the overall survival of READ in the high-risk group score was lower. Moreover, the risk model has high predictive value and good predictive capacity in predicting the long-term prognosis of READ. Immune heterogeneity and somatic mutation specificity were also found in different risk groups. Immunotherapy could potentially provide greater benefits for the high-risk group. Conclusion: Explored the prognostic value and potential mechanism of genes related to fatty acid metabolism/ferroptosis in READ, which is helpful to deepen the understanding of the pathological mechanism of patients and lay a theoretical foundation for subsequent research and treatment.

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The hepatoprotective effects of n3-polyunsaturated fatty acids against non-alcoholic fatty liver disease in diabetic rats through the FOXO1/PPARα/GABARAPL1 signalling pathway

Cited by 9 publications

References 66 publications

Insulin Inhibits Autophagy by Inhibiting the Binding of FoXO1 to the Promoter Region of GABARAPL1

Insulin Inhibits Autophagy by Inhibiting the Binding of FoXO1 to the Promoter Region of GABARAPL1

Multipanel Approach including miRNAs, Inflammatory Markers, and Depressive Symptoms for Metabolic Dysfunction-Associated Steatotic Liver Disease Diagnosis during 2-Year Nutritional Intervention

Construct a prognostic model based on fatty acid metabolism/ferroptosis-related genes and reveal the immune heterogeneity and somatic mutation specificity of rectal adenocarcinoma in different groups

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