Thyroid Hormone Decreases Hepatic Steatosis, Inflammation, and Fibrosis in a Dietary Mouse Model of Nonalcoholic Steatohepatitis

Zhou, Jin; Tripathi, Madhulika; Ho, Jia Pei; Widjaja, Anissa A.; Shekeran, Shamini Guna; Camat, Macalinao Dominique; James, Anne; Wu, Yajun; Ching, Jianhong; Kovalik, Jean‐Paul; Lim, Kiat-Hon; Cook, Stuart A.; Bay, Boon‐Huat; Singh, Brijesh Kumar; Yen, Paul M.

doi:10.1089/thy.2021.0621

Cited by 48 publications

(33 citation statements)

References 39 publications

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“…In accordance with previously established mass spectrometry (MS)based methods, liver samples were used for quantitative determination of targeted metabolite levels for CEs, triacylglycerols, DAGs, and MAGs by the Metabolomics Core Facility of Duke-NUS Medical School 49 . Liver tissue was homogenized in 50% acetonitrile and 0.3% formic acid.…”

Section: Metabolomics Profiling Of Lipid Metabolites In the Livermentioning

confidence: 99%

Spermidine-mediated hypusination of translation factor EIF5A improves mitochondrial fatty acid oxidation and prevents non-alcoholic steatohepatitis progression

et al. 2022

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Spermidine is a natural polyamine that has health benefits and extends life span in several species. Deoxyhypusine synthase (DHPS) and deoxyhypusine hydroxylase (DOHH) are key enzymes that utilize spermidine to catalyze the post-translational hypusination of the translation factor EIF5A (EIF5AH). Here, we have found that hepatic DOHH mRNA expression is decreased in patients and mice with non-alcoholic steatohepatitis (NASH), and hepatic cells treated with fatty acids. The mouse and cell culture models of NASH have concomitant decreases in Eif5aH and mitochondrial protein synthesis which leads to lower mitochondrial activity and fatty acid β-oxidation. Spermidine treatment restores EIF5AH, partially restores protein synthesis and mitochondrial function in NASH, and prevents NASH progression in vivo. Thus, the disrupted DHPS-DOHH-EIF5AH pathway during NASH represents a therapeutic target to increase hepatic protein synthesis and mitochondrial fatty acid oxidation (FAO) and prevent NASH progression.

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Section: Metabolomics Profiling Of Lipid Metabolites In the Livermentioning

confidence: 99%

Spermidine-mediated hypusination of translation factor EIF5A improves mitochondrial fatty acid oxidation and prevents non-alcoholic steatohepatitis progression

et al. 2022

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“…liver [11,12]. NAFLD caused by hypothyroidism is usually attributed to interruption of TH signaling, resulting in decreased lipid utilization by the liver [13,14].…”

Section: Discussionmentioning

confidence: 99%

Effect of Liraglutide on Serum TSH Levels in Patients with NAFLD and its Underlying Mechanisms

Wen

et al. 2022

International Journal of Clinical Practice

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This study aimed to evaluate the effect of liraglutide on serum thyroid-stimulating hormone (TSH) levels in patients with type 2 diabetes mellitus (T2DM) and explore the underlying mechanisms via bioinformatics analysis. A total of 49 obese/overweight patients with T2DM received liraglutide during outpatient visits or hospitalization in the Department of Endocrinology. Meanwhile, the control group included 49 patients with T2DM but without nonalcoholic fatty liver disease (NAFLD) who were matched for age and sex (baseline from July 2016 to June 2021). Follow-up data on the last use of liraglutide were also retrieved. Age, sex, body mass index (BMI), and duration of diabetes were obtained from the participants’ records. All patients were tested for biochemical markers hemoglobin A1c (HbA1c), alanine transaminase, aspartate transaminase, free triiodothyronine, free thyroxine (FT4), and TSH at baseline and follow-up. After adjusting for all factors with a p -value < 0.05, BMI, HbA1c, LDL, FT4, and TSH were identified as significant independent risk factors for NAFLD in the univariate analysis. Following liraglutide therapy (average time 16 months), these patients had significantly lower BMI, HbA1c, and TSH but higher high-density lipoprotein (HDL) levels than those in the baseline data (all p < 0.05), and further subgroup analysis stratified by duration of liraglutide use showed that the test for time trends had statistical differences in BMI and TSH but not in HbA1c and HDL. After the therapy, the NAFLD and NASH groups showed significantly decreased TSH levels after liraglutide therapy compared with the corresponding baseline data. Furthermore, the expression of THRB, which encodes TRβ, was significantly decreased in the NAFLD group, which may explain the thyroid hormone resistance-like manifestation in the clinical findings. In conclusion, liraglutide improves hepatic thyroid hormone resistance in T2DM with NAFLD, and restoration of impaired TRβ expression in NAFLD is a potential mechanism involved in the process of liraglutide therapy.

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“…In fact, evidence of a higher prevalence of NAFLD in patients with hypothyroidism has been detailed recorded in previous literature ( 23 , 31 ). Thyroid hormones mainly activate TH-Receptor β, a potential target in NAFLD therapy, and thus may improve liver steatosis ( 32 , 33 ). DEHP may lead to thyroid function disorder since DEHP possessed thyroid receptor (TR) antagonist activity ( 34 ).…”

Section: Discussionmentioning

confidence: 99%

Associations of phthalates with NAFLD and liver fibrosis: A nationally representative cross-sectional study from NHANES 2017 to 2018

Chen

Tian

et al. 2022

Front. Nutr.

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ObjectiveAlthough phthalates are common environmental pollutants, few studies have focused on the relationship of phthalates exposure with non-alcoholic fatty liver disease (NAFLD) or liver fibrosis, and especially, the alternative phthalates have been questioned in recent years about whether they are better choices. Thus, this study aimed to explore the associations of exposure to major phthalates or alternative phthalates with NAFLD and liver fibrosis.MethodsData of 1450 adults from the National Health and Nutrition Examination Survey (NHANES) 2017-2018 were collected. The urinary metabolite concentrations of di-2-ethylhexyl phthalate (DEHP), diisononyl phthalate (DINP) and diisodecyl phthalate (DIDP) were detected. Controlled attenuation parameter (CAP) and median liver stiffness measurement (LSM) were acquired for quantitative diagnosis of NAFLD and liver fibrosis by vibration-controlled transient elastography. Multivariate logistic regression analysis and linear regression analysis were performed to examine the associations between phthalates and NAFLD and liver fibrosis.ResultsAfter adjustment of the potential factors, the prevalence of NAFLD was significantly elevated among those in the fourth quartile of mono-(2-ethyl-5-carboxypentyl) phthalate (OR, 95%CI = 2.719, 1.296, 5.700, P = 0.016), mono (2-ethyl-5-hydroxyhexyl) phthalate (OR, 95%CI = 2.073, 1.111, 3.867, P = 0.037). No significant association was found between the alternative phthalates and NAFLD. The similar result was gained by linear regression analysis that MECPP was still significantly associated with Ln CAP (Q4 vs. Q1: β, 95%CI = 0.067, 0.017, 0.118, P = 0.027). After adjustment for the same covariates, no significant association between phthalates and liver fibrosis was found in logistics regression analysis.ConclusionsAll in all, higher prevalence of NAFLD is correlated with DEHP but not DINP or DIDP in American adults. There is no significant relationship between phthalates and liver fibrosis defined as LSM ≥ 8 Kpa. Nevertheless, further research is needed to provide evidence of causality.

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Thyroid Hormone Decreases Hepatic Steatosis, Inflammation, and Fibrosis in a Dietary Mouse Model of Nonalcoholic Steatohepatitis

Cited by 48 publications

References 39 publications

Spermidine-mediated hypusination of translation factor EIF5A improves mitochondrial fatty acid oxidation and prevents non-alcoholic steatohepatitis progression

Spermidine-mediated hypusination of translation factor EIF5A improves mitochondrial fatty acid oxidation and prevents non-alcoholic steatohepatitis progression

Effect of Liraglutide on Serum TSH Levels in Patients with NAFLD and its Underlying Mechanisms

Associations of phthalates with NAFLD and liver fibrosis: A nationally representative cross-sectional study from NHANES 2017 to 2018

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