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Non-alcoholic fatty liver disease severity is modulated by transglutaminase type 2.

ABSTRACT: Non-alcoholic fatty liver disease (NAFLD) is one of the most important liver diseases worldwide. Currently, no effective treatment is available, and NAFLD pathogenesis is incompletely understood. Transglutaminase type 2 (TG2) is a ubiquitous enzyme whose dysregulation is implicated in the pathogenesis of various human diseases. Here we examined the impact of TG2 on NAFLD progression using the high-fat-diet-induced model in both wild-type and TG2-deficient mice. Animals were fed with a standard chow diet or a high-fat diet (42% of the energy from fat) for 16 weeks. Results demonstrated that the absence of a functional enzyme, which causes the impairment of autophagy/mitophagy, leads to worsening of disease progression. Data were confirmed by pharmacological inhibition of TG2 in WT animals. In addition, the analysis of human liver samples from NAFLD patients validated the enzyme's involvement in the liver fat disease pathogenesis. Our findings strongly suggest that TG2 activation may offer protection in the context of NAFLD, thus representing a novel therapeutic target for tackling the NAFLD progression.

SUBMITTER: Piacentini M

PROVIDER: S-EPMC5833377 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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Non-alcoholic fatty liver disease severity is modulated by transglutaminase type 2.

Piacentini Mauro M Baiocchini Andrea A Del Nonno Franca F Melino Gerry G Barlev Nickolai A NA Rossin Federica F D'Eletto Manuela M Falasca Laura L

Cell death & disease 20180215 3

Non-alcoholic fatty liver disease (NAFLD) is one of the most important liver diseases worldwide. Currently, no effective treatment is available, and NAFLD pathogenesis is incompletely understood. Transglutaminase type 2 (TG2) is a ubiquitous enzyme whose dysregulation is implicated in the pathogenesis of various human diseases. Here we examined the impact of TG2 on NAFLD progression using the high-fat-diet-induced model in both wild-type and TG2-deficient mice. Animals were fed with a standard c ...[more]

PMID: 29449533

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Project description:BackgroundNut consumption has been associated with reduced inflammation, insulin resistance, and oxidative stress. However, the influence on the prevalence and severity of non-alcoholic fatty liver disease (NAFLD) has yet to be evaluated.Methods4655 subjects were included as part of a colorectal carcinoma screening program (SAKKOPI) between 07/2010 and 07/2019 and analyzed 2020. Patients were characterized using biochemical and metabolic parameters, as well as a detailed questionnaire on dietary habits. The diagnosis of NAFLD was established using abdominal ultrasound. Consumption of nuts was graded as: no consumption or <1 time/week, 1-6 times/week, 1 time/day and ≥2 times/day.ResultsMean age was 58.5±9.8years with a mean BMI of 26.5±4.7kg/m2. 2058 (44.2%) patients suffered from the metabolic syndrome, 2407 (51.6%) had arterial hypertension, 2287 (49.1%) showed prediabetes/diabetes, 1854 (39.4%) had dyslipidemia and 1984 patients (43.5%) were diagnosed with NAFLD. Prevalence of metabolic syndrome (1219 [48.7%] vs. 605 [40.2%] vs. 189 [37.4%] vs. 45 [31.7%], p<0.001) and NALFD (1184 [48.1%] vs. 594 [40.7%] vs. 158 [31.7%] vs. 48 [34.0%], p<0.001). On multivariable logistic regression analysis adjusting for potential confounders and dietary patterns, nut consumption ≥1time/day was inversely associated with NAFLD in the overall cohort (adjusted Odds ratio[aOR]: 0.719 [95%CI:0.558-0.926], p = 0.011). However, following subgroup analysis, this inverse association was only confirmed in male patients (aOR: 0.589 [95%CI: 0.411-0.844], p = 0.004) but not in females (aOR: 0.886 [95%CI: 0.616-1.275], p = 0.515). Moreover, patients who consumed nuts 1-6 times/week had a significantly lower prevalence of advanced fibrosis (Fib-4 score >2.67: aOR: 0.551 [95%CI: 0.338-0.898], p = 0.017; Forns-Index >6.9: aOR: 0.585 [95%CI: 0.402-0.850], p = 0.005).ConclusionsNut consumption might exert beneficial effects on the prevalence of NAFLD in males. The negative association with advanced fibrosis warrants further investigation.

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Non-alcoholic fatty liver disease severity is modulated by transglutaminase type 2.

Publications

Non-alcoholic fatty liver disease severity is modulated by transglutaminase type 2.

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