Non-alcoholic fatty liver disease across the spectrum of hypothyroidism

Chung, Gyung Ho; Kim, Dong‐Hee; Kim, Won; Yim, Jeong Yoon; Park, Min Jung; Kim, Yoon Jun; Yoon, Jung‐Hwan; Lee, Hyo Suk

doi:10.1016/j.jhep.2012.02.027

Cited by 265 publications

(253 citation statements)

References 39 publications

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“…These observations reveal the complex role of the thyroid hormones on fibrosis that could depend on the type of insult or tissue examined. In the case of the liver, and in agreement with our results, a TRβ selective analog was effective at reducing hepatic disease and carcinogenesis in rodents (28,29,32). Although the natural hormone and TR agonists present adverse effects (21,24), novel thyromimetic drugs with fewer adverse effects might be potentially developed and used to block the progression of fibrotic diseases.…”

Section: Discussionsupporting

confidence: 87%

“…Thus, it has been reported that hypothyroidism induced by antithyroidal drugs can prevent pulmonary and cutaneous fibrosis induced by hypochlorous acid (51) and to improve survival after acute thioacetamide administration in the rat (52). However, hypothyroidism also induces cardiac fibrosis in the rat (53,54), thyroid hormone administration ameliorates kidney fibrosis (55), and thyroid disfunction and subclinical hypothyroidism have been associated with primary biliary cirrhosis, primary sclerosing cholangitis, and nonalcoholic fatty liver disease in humans (29,32). These observations reveal the complex role of the thyroid hormones on fibrosis that could depend on the type of insult or tissue examined.…”

Section: Discussionmentioning

confidence: 99%

“…TRβ mediates the majority of the actions of T3 in the liver (23), playing an important role in regulating metabolism (24,25), regeneration (26), senescence (27), and carcinogenesis (28). Recent findings suggest that nonalcoholic fatty liver disease, which can progress to liver fibrosis, cirrhosis, and hepatocellular carcinoma, is associated with impaired thyroid action in the liver (29)(30)(31)(32). We have shown that expression of TRβ1 in liver cancer cells represses TGF-β-mediated proliferation and induction of metalloproteases (33), suggesting that the receptor could antagonize the response to the growth factor and, therefore, influence carcinogenesis.…”

mentioning

confidence: 99%

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Thyroid hormones inhibit TGF-β signaling and attenuate fibrotic responses

Alonso-Merino

Orozco

Ruíz-Llorente

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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TGF-β, the most potent profibrogenic factor, acts by activating SMAD (mothers against decapentaplegic) transcription factors, which bind to SMAD-binding elements in target genes. Here, we show that the thyroid hormone triiodothyronine (T3), through binding to its nuclear receptors (TRs), is able to antagonize transcriptional activation by TGF-β/SMAD. This antagonism involves reduced phosphorylation of SMADs and a direct interaction of the receptors with SMAD3 and SMAD4 that is independent of T3-mediated transcriptional activity but requires residues in the receptor DNA binding domain. T3 reduces occupancy of SMADbinding elements in response to TGF-β, reducing histone acetylation and inhibiting transcription. In agreement with this transcriptional cross-talk, T3 is able to antagonize fibrotic processes in vivo. Liver fibrosis induced by carbon tetrachloride is attenuated by thyroid hormone administration to mice, whereas aged TR knockout mice spontaneously accumulate collagen. Furthermore, skin fibrosis induced by bleomycin administration is also reduced by the thyroid hormones. These findings define an important function of the thyroid hormone receptors and suggest TR ligands could have beneficial effects to block the progression of fibrotic diseases.This work was supported by Grants BFU2011-28058 and BFU2014-53610P from Ministerio de Economía y Competitividad; S2011/BMD-2328 TIRONET from the Comunidad de Madrid; and RD12/0036/0030 from the Instituto de Salud Carlos III. The cost of this publication has been paid in part by FEDER fund

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Section: Discussionsupporting

confidence: 87%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Thyroid hormones inhibit TGF-β signaling and attenuate fibrotic responses

Alonso-Merino

Orozco

Ruíz-Llorente

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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“…Although some studies have reported associations of SCH with insulin resistance (7,8), metabolic syndrome (MS) (7,9), and CHD (10,11), not all previous findings have been consistent (12,13,14). Recent studies in adults (9,15,16) and children (7) have shown that SCH is closely associated with NAFLD independent of potential confounders. Based on these findings and considering that insulin resistance is a key feature of NAFLD, we hypothesized that the relationship of SCH with cardiometabolic risk factors and CHD may be influenced by the presence of increased intrahepatic fat.…”

mentioning

confidence: 99%

Fatty liver largely explains associations of subclinical hypothyroidism with insulin resistance, metabolic syndrome, and subclinical coronary atherosclerosis

Posadas‐Romero

Jorge‐Galarza

Posadas-Sánchez

et al. 2014

European Journal of Endocrinology

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Background: The association of subclinical hypothyroidism (SCH) with insulin resistance, metabolic syndrome (MS), and coronary atherosclerosis is uncertain. Objective: To investigate the role of increased intrahepatic fat in the association of SCH with insulin resistance, MS, and coronary atherosclerosis. Design, patients, and methods: We conducted a cross-sectional study in a sample of 753 subjects (46% males) aged 35-70 years with no history of diabetes, renal, hepatic, thyroid, or coronary heart disease, and were participants of the Genetics of Atherosclerotic Disease study. SCH was defined as a high serum TSH level with normal free thyroxine concentration. Fatty liver (FL), coronary artery calcification (CAC), and abdominal visceral adipose tissue were assessed by computed tomography. Cross-sectional associations of SCH with and without FL, with MS, insulin resistance, and subclinical atherosclerosis defined as a CAC score O0, were examined in logistic regression models. Results: SCH was observed in 17.7% of the population studied. The prevalence of FL was similar in both euthyroid and SCH subjects (31.8 vs 27.8%, PZ0.371). SCH plus FL subjects were heavier and had more metabolic abnormalities compared with SCH plus normal liver subjects. In multivariate-adjusted logistic regression analyses, SCH plus FL was associated with MS (odds ratio (OR): 2.73, 95% CI: 1.26-5.92), insulin resistance (OR: 4.91, 95% CI: 1.63-14.75), and CAC score O0 (OR: 3.05, 95% CI: 1.20-7.76). SCH without FL showed no associations. Conclusion: SCH with FL is associated with increased odds of MS, insulin resistance, and CAC, independent of potential confounders.

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“…Some tend to behave aggressive tactics in conducting screening from 35 years of age, every 5 years among high-risk groups, others such as the Royal College of Physicians and U.S. Preventive Services Task Force are limited by the fact that there is insufficient data for or against screening, therefore the active screening is not recommended [2].…”

Section: Introductionmentioning

confidence: 99%

Risk assessment of the subclinical hypothyroidism in non-alcoholic fatty liver disease patients with different levels of cardiovascular risk

Kolesnikova¹,

Nemtsova²,

Isayeva³

2017

Blood Heart Circ

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Objective: To assess the risk of developing subclinical hypothyroidism (SH) in patients with non-alcoholic fatty liver disease (NAFLD) with a different risk of cardiovascular complications, and to identify the link between high risk of developing SH and major cardiovascular factors (CV). Material and methods: A one-stage clinical trial included 298 people with NAFLD with the presence of one or more CV risk factors (arterial hypertension, smoking, hypercholesterolemia) and various levels of CV risk factors on the SCORE scale. All patients were questioned on a standard questionnaire and HRQ, a thyroid status study was conducted.Result: Patients were divided into three groups according to the level of total CV risk for SCORE: 33.9% had low / moderate CV risk, 41.9% -high and 24.2% -very high CV risk. The majority of the subjects were in the age groups 50-59 and 60-69 years. In the age group 40-49 years, 22.2% of patients had high CV risk, 28% of men aged 50-59 years had moderate CV risk, while 49.7% of older patients showed very high CV risk. According to the results of a survey on the HRQ questionnaire, a low risk of developing hypertension was found in 34.9%, a moderate risk in 48.9%, and a high risk was found in 16.1% of patients. Persons with a very high CV risk on the SCORE scale also have a high risk of developing the SH according to the HRQ questionnaire. Among patients with the presence of one or more of the above CV risk factors, early markers of thyroid status disorders should be identified and the risk of developing hypertension should be assessed. Such a tactic contributes to an adequate assessment of the risk of SH in patients with NAFLD and the development of methods for primary prevention.

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Non-alcoholic fatty liver disease across the spectrum of hypothyroidism

Cited by 265 publications

References 39 publications

Thyroid hormones inhibit TGF-β signaling and attenuate fibrotic responses

Thyroid hormones inhibit TGF-β signaling and attenuate fibrotic responses

Fatty liver largely explains associations of subclinical hypothyroidism with insulin resistance, metabolic syndrome, and subclinical coronary atherosclerosis

Risk assessment of the subclinical hypothyroidism in non-alcoholic fatty liver disease patients with different levels of cardiovascular risk

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