Association of non-alcoholic fatty liver disease with thyroid function: A systematic review and meta-analysis

Guo, Zeqi; Li, Miaomiao; Han, Bing; Qi, Xingshun

doi:10.1016/j.dld.2018.08.012

Cited by 122 publications

(106 citation statements)

References 44 publications

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“…Liver is one of the major target tissues of TH, and people with low thyroid function are closely associated with multiple liver-related diseases. The cross-sectional and systemic view studies indicated that subclinical hypothyroidism, and even in the upper normal limit of TSH levels were significantly associated with the risk of NAFLD and advanced fibrosis [166][167][168][169]. Interestingly, high level of TSH itself may be an important risk factor points to the pathogenesis of NAFLD, independent of thyroid hormones [168,169], and the supplementation of levothyroxine shows clear benefits on NAFLD in subclinical-and mild subclinical-hypothyroidism patients with dyslipidemia [170].…”

Section: Resultsmentioning

confidence: 99%

“…The cross-sectional and systemic view studies indicated that subclinical hypothyroidism, and even in the upper normal limit of TSH levels were significantly associated with the risk of NAFLD and advanced fibrosis [166][167][168][169]. Interestingly, high level of TSH itself may be an important risk factor points to the pathogenesis of NAFLD, independent of thyroid hormones [168,169], and the supplementation of levothyroxine shows clear benefits on NAFLD in subclinical-and mild subclinical-hypothyroidism patients with dyslipidemia [170]. Moreover, both in vitro and in vivo experiments demonstrated THs and THs analogs exhibit the potential therapeutic and preventive application in NAFLD and HCC [7,16,17,142,[145][146][147][148][149], highlighting the urgent need to understand the complex mechanisms underlying the effects of thyroid hormone.…”

Section: Resultsmentioning

confidence: 99%

“…GC-1 was the first synthetic THRB agonist that could be used as a scaffold compound for developing other TH derivatives, which are easily modified and synthesized more efficiently than native TH [168]. GC-1 binds all major isoforms of THRB with similar affinity to T 3.…”

Section: Potential Application Of Th and Analogs In Nafld And Hccmentioning

confidence: 99%

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Molecular functions and clinical impact of thyroid hormone-triggered autophagy in liver-related diseases

Chi

Tsai

et al. 2019

J Biomed Sci

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The liver is controlled by several metabolic hormones, including thyroid hormone, and characteristically displays high lysosomal activity as well as metabolic stress-triggered autophagy, which is stringently regulated by the levels of hormones and metabolites. Hepatic autophagy provides energy through catabolism of glucose, amino acids and free fatty acids for starved cells, facilitating the generation of new macromolecules and maintenance of the quantity and quality of cellular organelles, such as mitochondria. Dysregulation of autophagy and defective mitochondrial homeostasis contribute to hepatocyte injury and liver-related diseases, such as non-alcoholic fatty liver disease (NAFLD) and liver cancer. Thyroid hormones (TH) mediate several critical physiological processes including organ development, cell differentiation, metabolism and cell growth and maintenance. Accumulating evidence has revealed dysregulation of cellular TH activity as the underlying cause of several liver-related diseases, including alcoholic or non-alcoholic fatty liver disease and liver cancer. Data from epidemiologic, animal and clinical studies collectively support preventive functions of THs in liver-related diseases, highlighting the therapeutic potential of TH analogs. Elucidation of the molecular mechanisms and downstream targets of TH should thus facilitate the development of therapeutic strategies for a number of major public health issues. Here, we have reviewed recent studies focusing on the involvement of THs in hepatic homeostasis through induction of autophagy and their implications in liver-related diseases. Additionally, the potential underlying molecular pathways and therapeutic applications of THs in NAFLD and HCC are discussed.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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Molecular functions and clinical impact of thyroid hormone-triggered autophagy in liver-related diseases

Chi

Tsai

et al. 2019

J Biomed Sci

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“…Nonalcoholic fatty liver disease (NAFLD) covers a wide range of hepatic changes, ranging from simple steatosis to non-alcoholic steato-hepatitis (NASH), liver cirrhosis and hepatocellular carcinoma and is one of the most common chronic liver disorders worldwide [1, 3,5]. It is associated with diverse clinical conditions including but not limited to obesity, renal failure, osteoporosis, type 2 diabetes, myocardial infarction, hypothyroidism, male infertility among others [5,6,8,[21][22][23][24][25]. Current therapies for this condition however remain unsatisfactory underscoring the need for discovering new efficacious treatments for this condition [12,13,26].…”

Section: Discussionmentioning

confidence: 99%

Hepatoprotective effects ofErythrina abyssinicaLam Ex Dc against Non Alcoholic Fatty Liver Disease in Sprague Dawley Rats

Yenesew

et al. 2019

Preprint

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Background: Non-alcoholic fatty liver disease (NFLD) is the hepatic manifestation of the metabolic syndrome recognized as the most prevalent chronic liver disease across all age groups. NFLD is strongly associated with obesity, insulin resistance, hypertension and dyslipidemia. Extensive research efforts are geared, through pharmacological approach, towards preventing or reversing this. Erythrina abyssinica Lam ex DC is an indigenous tree used widely used in traditional medicine, including for the treatment of liver related diseases, and has been shown to possess hypoglycemic, anti-oxidant, antimicrobial and anti-plasmodia effects. The present study is aimed at establishing the effects of E. abyssinica on the development of Non-alcoholic fatty liver disease induced by a high-fat and high-sugar diet in rats, in-vivo model. (40) were randomly divided into five groups: positive control (pioglitazone), Negative control (high fat/high sugar diet), low test dose (200 mg/kg), high test dose (400 mg/kg) and normal group (standard chow pellets and fresh water). Methods: Forty ratsThe inhibitory effect of the stem bark extract of E. abyssinica on the development of NAFLD was evaluated by chronic administration the herb extracts to rats on a high-fat/high-sugar diet.Biochemical indices of hepatic function including serum lipid profile, serum aspartate transaminase and alanine transaminase levels were then determined. Histological analysis of liver samples was carried out to quantify the degree of steato-hepatitis. Liver weights were taken and used to determine the hepatic index. The data was analyzed using one-way ANOVA, and Tukey's post-hoc tests were done in cases of significance. Histology data was analyzed using Kruskal-Wallis and Dunn's post-hoc test was done in cases of significance. Significance was set at p<0.05. Results:The freeze dried extract of E. abyssinica had significant effects on fasting blood glucose [5.43 ± 0.17 (HF/HSD) vs 3.8 ± 0.15 (E 400 mg/kg) vs 4.54 ± 0.09 (E 200 mg/kg) vs. 4.16 ± 0.13 (PIOG) vs. 2.91 ± 0.16 (normal control): P value < 0.0001], and insulin sensitivity [329.4 ± 13.48 mmol/L · min (HF/HSD) vs. 189.8 ± 12.11 mmol/L · min (E 400 mg/kg) vs. 233.8 ± 6.55 mmol/L · min (E 200 mg/kg) vs. 211.1 ± 7.35 mmol/L · min (PIOG) vs. 142.9 ± 11.94 mmol/L · min: P value < 0.0001],The extract had significant effects on hepatic indices including, hepatic triglycerides (P value < 0.0001), liver weights (P value < 0.0001), liver weight-body weight ratio (P value < 0.0001), serum ALT levels (P value < 0.0001), serum AST (P value < 0.0017), serum total cholesterol (P value < 0.0001), serum triglycerides (P value < 0.0001), and serum LDL-cholesterol (P value < 0.0001). The extracts however showed no significant effects on HDL-cholesterol (P value = 0.4759).Histological analysis showed that the extract appears to possess protective effects against steatosis, inflammation and hepatic ballooning, with the high dose (400mg/kg) being more hepatoprotective. Conclusion:The freeze dried stem bark extract of Eryth...

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“…(2) Numerous studies have shown an inverse relationship between serum TH levels and NAFLD given that patients with hypothyroidism and subclinical hypothyroidism have increased risk for NAFLD and vice versa. (3) Transcriptomes of liver samples obtained from bariatric surgery patients also showed that the most prominent altered gene set was associated with TH action. (4) Additionally, T 3 and several thyromimetics decreased intrahepatic triglycerides in rodent models of hepatosteatosis.…”

Section: Thyroid Hormones and Thyromimetics: A New Approach To Nonalcmentioning

confidence: 99%

Thyroid Hormones and Thyromimetics: A New Approach to Nonalcoholic Steatohepatitis?

et al. 2020

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Association of non-alcoholic fatty liver disease with thyroid function: A systematic review and meta-analysis

Cited by 122 publications

References 44 publications

Molecular functions and clinical impact of thyroid hormone-triggered autophagy in liver-related diseases

Molecular functions and clinical impact of thyroid hormone-triggered autophagy in liver-related diseases

Hepatoprotective effects ofErythrina abyssinicaLam Ex Dc against Non Alcoholic Fatty Liver Disease in Sprague Dawley Rats

Thyroid Hormones and Thyromimetics: A New Approach to Nonalcoholic Steatohepatitis?

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