Non-alcoholic fatty liver disease and thyroid dysfunction: A systematic review

Eshraghian, Ahad; Jahromi, Alireza Hamidian

doi:10.3748/wjg.v20.i25.8102

Cited by 124 publications

(126 citation statements)

References 66 publications

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“…Based on our findings, we suggested hormone disturbance as an important underlying driving force of NAFLD pathogenesis instead of the special diet. Previous studies also suggested that TH, estrogen, and GH were related to NAFLD and played roles in regulation of hepatic steatosis [16,46,54]. The results of these studies supported the present study in that they demonstrated the important role of hormones regulation in development of NAFLD.…”

Section: Discussionsupporting

confidence: 81%

Decreased Hepatic Lactotransferrin Induces Hepatic Steatosis in Chronic Non-Alcoholic Fatty Liver Disease Model

Lee

Son

Jeon

et al. 2018

Cell Physiol Biochem

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Background/Aims: Non-alcoholic fatty liver disease (NAFLD) is an emerging metabolic disease. Although it leads to severe hepatic diseases including steatohepatitis, cirrhosis, and hepatic cancer, little is known about therapy to prevent and cure hepatic steatosis, the first step of NAFLD. We conducted this investigation to unveil the mechanism of hepatic steatosis. Methods: We established a novel chronic NAFLD mouse model through whole body irradiation and verified the model through histological and biochemical analysis. To find molecular mechanism for hepatic steatosis, we analyzed hepatic transcriptomic profiles in this model and selected target molecule. To induce the expression of lactotransferrin (Ltf) and regulate the NAFLD, growth hormone (GH) and coumestrol was introduced to hepatocyte and mice. The universal effect of coumestrol was confirmed by administration of coumestrol to NAFLD mouse model induced by high-fructose, high-fat, and MCD diet. Results: It was observed that decreased hepatic Ltf expression led to excessive hepatic lipid accumulation in NAFLD mouse. Furthermore, we found that GH was decreased in irradiated mice and functioned as an upstream regulator of Ltf expression. It was observed that GH could stimulate Ltf expression and prevent uptake of dietary lipids in hepatocytes, leading to rescue of NAFLD. Finally, we suggested that coumestrol, a kind of isoflavonoid, could be used as an inducer of hepatic Ltf expression through cooperation with the GH signaling pathway both in vitro and in vivo. Conclusions: Hepatic Ltf prevents hepatic steatosis through inhibition of dietary lipid uptake in radiation-induced NAFLD mouse model. We also suggest coumestrol as a drug candidate for prevention of NAFLD.

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Section: Discussionsupporting

confidence: 81%

Decreased Hepatic Lactotransferrin Induces Hepatic Steatosis in Chronic Non-Alcoholic Fatty Liver Disease Model

Lee

Son

Jeon

et al. 2018

Cell Physiol Biochem

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“…This indicates that hypothyroidism may directly result in NAFLD irrespective of other metabolic risk factors. Considering the results of these studies, hypothyroidism may be added to risk factors of NAFLD (28). The findings of our study were correlated with a study done by Chung et al who concluded that subclinical hypothyroidism, even in the range of upper normal TSH levels, was found to be related to NAFLD in a dosedependent manner.…”

Section: Discussionsupporting

confidence: 80%

“…However, NAFLD patients were more likely to have low TSH levels although hypothyroidism and hyperthyroidism were not associated with NAFLD. The observed changes in TSH and free T3 levels may attribute to alterations in thyroid hormones due to sick euthyroid syndrome in NAFLD (28,43).…”

Section: Discussionmentioning

confidence: 99%

Association and impact of non-alcoholic fatty liver disease on thyroid function

2017

Int. J. Curr. Res. Med. Sci.

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Nonalcoholic fatty liver disease (NAFLD) means accumulation of fat mainly triglyceride exceeding 5 % of liver weight, affecting approximately 20% of population in developed countries. Thyroid dysfunction have been frequently associated with non-alcoholic fatty liver disease. The aim of this study is to determine any association between nonalcoholic fatty liver disease and thyroid dysfunction and to evaluate the impact of non-alcoholic fatty liver disease on thyroid function tests. Subjects and methods: This study was carried out on sixty adult men and women with nonalcoholic fatty liver disease and sixty age-and sex-matched males and females without the disease. NAFLD patients were subjected to a full assessment of medical history, physical examination, abdominal ultrasonography as well as routine laboratory tests. Patients and controls underwent liver function and thyroid function testing including thyroid antibodies. Results: Thirteen patients with NAFLD (21.7%) were found to have thyroid dysfunction. The most common thyroid dysfunction was subclinical hypothyroidism which was found in 10 (16.7%) NAFLD patients followed by overt hypothyroidism in 3 patients (5%). There were statistically significant difference between patients and controls as regard to TSH (p=0.0001), FT4 (p=0.005), FT3 (P=0.043), anti-TPO (p=0.047), anti-TG (p=0.001), IR (p=0.024), insulin (p=0.002), and Leptin (p=0.002). TSH concentration was significantly correlated with ALT (r= 0.381), GGT (r=0.354), HbA1C (r=0.288), triglyceride (r=0.368), FT4 (r=0.414), FT3(r=0.231), anti-TPO(r=0.298), serum insulin (r= 0.287), insulin resistance (IR) (r= 0.453), and serum Leptin (r=0.360) levels.In our patients, hepatic steatosis in the form of increased liver echogenecity was present in almost all patients (100%), and hepatomegaly in twenty-four patients (40%). Thus. Hepatic steatosis were correlated significantly with ALT, GGT, HbA1C, triglyceride, HDL-C, TSH, FT4, FT3, anti-TPO, anti-TG, serum insulin, insulin resistance (IR), and serum Leptin. Conclusion: Thyroid dysfunctions are common in NAFLD patients, with subclinical hypothyroidism hypothyroidism being the most prevalent one. Hepatic steatosis has shown an evident positive correlation with elevated TSH as well as thyroid autoantibodies.

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“…In this study, there were a 40% increased risk of NAFLD in individuals with TSH between 2.5-4.5 mIU/L compared to individuals with TSH lower than 2.5 mIU/L, which still yield more controversy regarding the never-ending discussion of whether to treat or not subclinical hypothyroidism. A systematic review found a 15.2% to 36.3% prevalence of hypothyroidism in patients with NAFLD/NASH and concluded that hypothyroidism should be added to risk factors of NAFLD/NASH (18). What remains to be known is if hypothyroidism predicts or not the severity of fatty liver disease, since different studies yielded controversial results (17)(18)(19)(20).…”

mentioning

confidence: 99%

“…A systematic review found a 15.2% to 36.3% prevalence of hypothyroidism in patients with NAFLD/NASH and concluded that hypothyroidism should be added to risk factors of NAFLD/NASH (18). What remains to be known is if hypothyroidism predicts or not the severity of fatty liver disease, since different studies yielded controversial results (17)(18)(19)(20). Interestingly, however, is the possible role of oxidative stress and mitochondrial dysfunction in the pathogenesis of NASH.…”

mentioning

confidence: 99%

Elevated irisin and alanine aminotransferase levels in hypothyroidism: role of oxidative stress?

Halpern

2016

Arch. Endocrinol. Metab.

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I n this issue of Archives of Endocrinology and Metabolism, two articles help to increase our knowledge about the connections between thyroid status and energy metabolism. Although the relation between thyroid disease with obesity and metabolic dysfunction has been well established for many decades, some of their linking mechanisms are surprisingly still poorly understood.In the first paper, a cross-sectional observational study, Ates and cols.(1) measured irisin levels of 37 patients with newly diagnosed hypothyroidism (and a mean TSH of 13.1 mIU/L) and 37 healthy volunteers.Irisin is a recently identified proliferator-activated receptor-gamma coactivator-1α (PGC-1α)-dependent myokine that drives browning of white fat via elevation of uncoupling protein-1 (UCP-1), leading to thermogenesis and metabolic improvement (2). It was demonstrated to be a cleavage product of the extracellular portion of type I membrane protein fibronectin type III domain containing 5 (FNDC5), that is released after physical activity. The isolation of irisin in 2012 led to a great rush in understanding its function and metabolic relevance, as it was initially considered one of the main drivers of the beneficial effects of exercise (2,3). However, its impact was weakened by further studies that questioned the metabolic relevance of irisin in humans since there is a substantial controversy whether humans are able to cleave the protein FNDC5 (4,5). This would happen due to humans have a truncated form of FNDC5 gene, and as a result, irisin levels be insignificant, and its detection in serum would be due to analytical interferences. Even though this theory is up to this time a matter of debate, many publications about irisin have arisen in the last years, both in animals and humans.Another disappointment about the potential role of irisin in metabolic improvement (and maybe as a potential therapeutic agent) was the observation that obese individuals and patients with metabolic syndrome have higher levels of irisin and that weight loss (regardless of whether through caloric restriction or bariatric surgery) leads to a decrease in irisin levels (6-8). Could this phenomenon be due to an "irisin resistance" analogous to insulin or leptin resistance or it could be due to a defense against metabolic impairment? These are questions still unanswered, and the first study in this journal issue points in the same controversial direction, demonstrating higher levels of irisin in hypothyroid patients (1). In the study, the mean BMI was not statistically different between groups (27.77 vs 26.11 kg/m 2 , in hypothyroid and control groups, respectively) and the main parameters associated with irisin levels were age, TSH and free T4 levels. On one hand, these results are in agreement with a study in a murine model of thyroid dysfunction, in which an upregulation of irisin levels in both hyper and hypothyroid rats, as well as a positive correlation between irisin and

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Non-alcoholic fatty liver disease and thyroid dysfunction: A systematic review

Cited by 124 publications

References 66 publications

Decreased Hepatic Lactotransferrin Induces Hepatic Steatosis in Chronic Non-Alcoholic Fatty Liver Disease Model

Decreased Hepatic Lactotransferrin Induces Hepatic Steatosis in Chronic Non-Alcoholic Fatty Liver Disease Model

Association and impact of non-alcoholic fatty liver disease on thyroid function

Elevated irisin and alanine aminotransferase levels in hypothyroidism: role of oxidative stress?

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