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: 2023-02-19

Papper version: info:eu-repo/semantics/acceptedVersion

Link to the original source: https://www.nature.com/articles/ijo201673

Licence document URL: http://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

Article's DOI: 10.1038/ijo.2016.73

Entity: Universitat Rovira i Virgili

Journal publication year: 2016

Publication Type: Journal Publications