Articles producció científica> Medicina i Cirurgia

Reduced circulating levels of sTWEAK are associated with NAFLD and may affect hepatocyte triglyceride accumulation

  • Identification data

    Identifier: imarina:6388729
    Authors:
    Lozano-Bartolomé JLlauradó GRodriguez MFernandez-Real JGarcia-Fontgivell JPuig JMaymó-Masip EVendrell JChacón M
    Abstract:
    © 2016 Macmillan Publishers Limited. Context: Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome and is strongly associated with obesity, dyslipidaemia and altered glucose regulation. Previous data demonstrated that low circulating levels of tumour necrosis factor weak inducer of apoptosis (sTWEAK) were associated with obesity, diabetes and insulin resistance, all traits associated with an increased risk of NALFD. Circulating sTWEAK levels are expected to be reduced in the presence of NAFLD. Objective: We aimed to explore the relationship between NAFLD and circulating sTWEAK levels in obese patients, and to evaluate the effect of sTWEAK on hepatocyte triglyceride accumulation. Design setting and patients: This is an observational case-control study performed in n=112 severely obese patients evaluated for NAFLD by abdominal ultrasound and n=32 non-obese patients without steatosis. Serum sTWEAK concentrations were measured by ELISA. Multivariable analyses were performed to determine the independent predictors of NAFLD. We analysed TWEAK and Fn14 protein expression in liver biopsies by western blotting and immunohistochemistry. An immortalized primary human hepatocyte cell line (HHL) was used to evaluate the effect of sTWEAK on triglyceride accumulation. Results: We observed a reduction in serum circulating sTWEAK concentrations with the presence of liver steatosis. On multivariable analysis, lower sTWEAK concentrations were independently associated with the presence of NAFLD (odds ratio (OR)=0.023; 95% confidence interval: 0.001-0.579; P<0.022). In human hepatocytes, sTWEAK administration reduced fat accumulation as demonstrated by the reduction in palmitic acid-induced accumulation of triglyceride and the decreased expression
  • Others:

    Author, as appears in the article.: Lozano-Bartolomé J; Llauradó G; Rodriguez M; Fernandez-Real J; Garcia-Fontgivell J; Puig J; Maymó-Masip E; Vendrell J; Chacón M
    Department: Medicina i Cirurgia Bioquímica i Biotecnologia
    URV's Author/s: Maymo Masip, Elsa / Rodríguez Chacón, Matilde / Vendrell Ortega, Juan José
    Keywords: Tweak Tnf-alpha Proinflammatory cytokine Ppar-gamma Metabolic disease High cardiovascular risk Hepatic insulin-resistance Fatty liver-disease Bariatric surgery Acid transporter cd36
    Abstract: © 2016 Macmillan Publishers Limited. Context: Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome and is strongly associated with obesity, dyslipidaemia and altered glucose regulation. Previous data demonstrated that low circulating levels of tumour necrosis factor weak inducer of apoptosis (sTWEAK) were associated with obesity, diabetes and insulin resistance, all traits associated with an increased risk of NALFD. Circulating sTWEAK levels are expected to be reduced in the presence of NAFLD. Objective: We aimed to explore the relationship between NAFLD and circulating sTWEAK levels in obese patients, and to evaluate the effect of sTWEAK on hepatocyte triglyceride accumulation. Design setting and patients: This is an observational case-control study performed in n=112 severely obese patients evaluated for NAFLD by abdominal ultrasound and n=32 non-obese patients without steatosis. Serum sTWEAK concentrations were measured by ELISA. Multivariable analyses were performed to determine the independent predictors of NAFLD. We analysed TWEAK and Fn14 protein expression in liver biopsies by western blotting and immunohistochemistry. An immortalized primary human hepatocyte cell line (HHL) was used to evaluate the effect of sTWEAK on triglyceride accumulation. Results: We observed a reduction in serum circulating sTWEAK concentrations with the presence of liver steatosis. On multivariable analysis, lower sTWEAK concentrations were independently associated with the presence of NAFLD (odds ratio (OR)=0.023; 95% confidence interval: 0.001-0.579; P<0.022). In human hepatocytes, sTWEAK administration reduced fat accumulation as demonstrated by the reduction in palmitic acid-induced accumulation of triglyceride and the decreased expression of cluster of differentiation 36 (CD36) and perilipin 1 and 2 (PLIN1 and PLIN2) genes. Conclusions: Decreased sTWEAK concentrations are independently associated with the presence of NAFLD. This is concordant with the observation that TWEAK reduces lipid accumulation in human liver cells.
    Thematic Areas: Serviço social Saúde coletiva Psicología Nutrition and dietetics Nutrition & dietetics Nutrição Medicine (miscellaneous) Medicina iii Medicina ii Medicina i Interdisciplinar General medicine Farmacia Enfermagem Endocrinology, diabetes and metabolism Endocrinology & metabolism Educação física Ciências biológicas ii Ciências biológicas i Ciência de alimentos Biotecnología Astronomia / física
    licence for use: https://creativecommons.org/licenses/by/3.0/es/
    ISSN: 03070565
    Author's mail: elsa.maymo@urv.cat matilde.rodriguez@urv.cat juanjose.vendrell@urv.cat
    Author identifier: 0000-0002-9133-3120 0000-0002-6994-6115
    Record's date: 2024-09-07
    Papper version: info:eu-repo/semantics/acceptedVersion
    Licence document URL: https://repositori.urv.cat/ca/proteccio-de-dades/
    Papper original source: International Journal Of Obesity. 40 (9): 1337-1345
    APA: Lozano-Bartolomé J; Llauradó G; Rodriguez M; Fernandez-Real J; Garcia-Fontgivell J; Puig J; Maymó-Masip E; Vendrell J; Chacón M (2016). Reduced circulating levels of sTWEAK are associated with NAFLD and may affect hepatocyte triglyceride accumulation. International Journal Of Obesity, 40(9), 1337-1345. DOI: 10.1038/ijo.2016.73
    Entity: Universitat Rovira i Virgili
    Journal publication year: 2016
    Publication Type: Journal Publications
  • Keywords:

    Endocrinology & Metabolism,Endocrinology, Diabetes and Metabolism,Medicine (Miscellaneous),Nutrition & Dietetics,Nutrition and Dietetics
    Tweak
    Tnf-alpha
    Proinflammatory cytokine
    Ppar-gamma
    Metabolic disease
    High cardiovascular risk
    Hepatic insulin-resistance
    Fatty liver-disease
    Bariatric surgery
    Acid transporter cd36
    Serviço social
    Saúde coletiva
    Psicología
    Nutrition and dietetics
    Nutrition & dietetics
    Nutrição
    Medicine (miscellaneous)
    Medicina iii
    Medicina ii
    Medicina i
    Interdisciplinar
    General medicine
    Farmacia
    Enfermagem
    Endocrinology, diabetes and metabolism
    Endocrinology & metabolism
    Educação física
    Ciências biológicas ii
    Ciências biológicas i
    Ciência de alimentos
    Biotecnología
    Astronomia / física
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