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Thyroid Function and the Risk of Non-Alcoholic Fatty Liver Disease in Morbid Obesity.

ABSTRACT: Background:An association between hypothyroidism and the risk of Non-alcoholic Fatty Liver Disease (NAFLD) has been suggested. This association remains to be elucidated in patients with morbid obesity. Aim:To evaluate the association between thyroid function and parameters of liver function and hepatic scores in patients with morbid obesity. Methods:Patients with morbid obesity followed in our center between January 2010 and July 2018 were included. The ones without evaluation of liver and thyroid functions were excluded. Fatty Liver Index (FLI) and BARD scores were used as predictors of hepatic steatosis and fibrosis, respectively. Results:We observed a positive association between TSH and both BARD (OR 1.14; p = 0.035) and FLI (OR 1.19; p = 0.010) in the unadjusted analysis. We found a negative association between free triiodothyronine levels and BARD (OR 0.70; p<0.01) and a positive association between free triiodothyronine levels and FLI (OR 1.48; p = 0.022). Concerning liver function, we found a positive association between total bilirubin and free thyroxine levels (? = 0.18 [0.02 to 0.35]; p = 0.033) and a negative association between total bilirubin and free triiodothyronine levels (? = -0.07 [-0.14 to -0.002]; p = 0.042). Conclusion:Higher levels of TSH and free triiodothyronine may be associated with a higher risk of NAFLD, particularly steatosis, in patients with morbid obesity.

SUBMITTER: Borges-Canha M

PROVIDER: S-EPMC7655985 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Thyroid Function and the Risk of Non-Alcoholic Fatty Liver Disease in Morbid Obesity.

Borges-Canha Marta M Neves João Sérgio JS Mendonça Fernando F Silva Maria Manuel MM Costa Cláudia C Cabral Pedro M PM Guerreiro Vanessa V Lourenço Rita R Meira Patrícia P Salazar Daniela D Ferreira Maria João MJ Pedro Jorge J Leite Ana A Von-Hafe Madalena M Vale Catarina C Viana Sara S Sande Ana A Belo Sandra S Lau Eva E Freitas Paula P Carvalho Davide D

Frontiers in endocrinology 20201028

<h4>Background</h4>An association between hypothyroidism and the risk of Non-alcoholic Fatty Liver Disease (NAFLD) has been suggested. This association remains to be elucidated in patients with morbid obesity.<h4>Aim</h4>To evaluate the association between thyroid function and parameters of liver function and hepatic scores in patients with morbid obesity.<h4>Methods</h4>Patients with morbid obesity followed in our center between January 2010 and July 2018 were included. The ones without evaluat ...[more]

PMID: 33193088

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Project description:Background & aims: Thrombospondin 1 (TSP1) is a multifunctional matricellular protein. We previously showed that TSP1 has an important role in obesity-associated metabolic complications, including inflammation, insulin resistance, cardiovascular, and renal disease. However, its contribution to obesity-associated non-alcoholic fatty liver disease/non-alcoholic steatohepatitis (NAFLD or NASH) remains largely unknown; thus, we aimed to determine its role.Methods: High-fat diet or AMLN (amylin liver NASH) diet-induced obese and insulin-resistant NAFLD/NASH mouse models were utilised, in addition to tissue-specific Tsp1-knockout mice, to determine the contribution of different cellular sources of obesity-induced TSP1 to NAFLD/NASH development.Results: Liver TSP1 levels were increased in experimental obese and insulin-resistant NAFLD/NASH mouse models as well as in obese patients with NASH. Moreover, TSP1 deletion in adipocytes did not protect mice from diet-induced NAFLD/NASH. However, myeloid/macrophage-specific TSP1 deletion protected mice against obesity-associated liver injury, accompanied by reduced liver inflammation and fibrosis. Importantly, this protection was independent of the levels of obesity and hepatic steatosis. Mechanistically, through an autocrine effect, macrophage-derived TSP1 suppressed Smpdl3b expression in liver, which amplified liver proinflammatory signalling (Toll-like receptor 4 signal pathway) and promoted NAFLD progression.Conclusions: Macrophage-derived TSP1 is a significant contributor to obesity-associated NAFLD/NASH development and progression and could serve as a therapeutic target for this disease.Lay summary: Obesity-associated non-alcoholic fatty liver disease is a most common chronic liver disease in the Western world and can progress to liver cirrhosis and cancer. No treatment is currently available for this disease. The present study reveals an important factor (macrophage-derived TSP1) that drives macrophage activation and non-alcoholic fatty liver disease development and progression and that could serve as a therapeutic target for non-alcoholic fatty liver disease/steatohepatitis.

Dataset Information

Thyroid Function and the Risk of Non-Alcoholic Fatty Liver Disease in Morbid Obesity.

Publications

Thyroid Function and the Risk of Non-Alcoholic Fatty Liver Disease in Morbid Obesity.

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