The SCAP/SREBP Pathway: A Mediator of Hepatic Steatosis

Moon, Young Ah

doi:10.3803/enm.2017.32.1.6

Cited by 89 publications

(78 citation statements)

References 20 publications

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“…11 Regarding insulin resistance, DM is strongly associated with NAFLD and subsequently with HCC. 12,13 Patients with DM commonly use statins because the prevalence of dyslipidemia is reported to be higher than in patients without DM. 14,15 However, the relationship between statins and HCC among patients with and without DM remains unclear.…”

Section: Introductionmentioning

confidence: 99%

Statin use and the risk of hepatocellular carcinoma in patients at high risk: A nationwide nested case-control study

Kim

Jang

Nam

et al. 2018

Journal of Hepatology

106

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Section: Introductionmentioning

confidence: 99%

Statin use and the risk of hepatocellular carcinoma in patients at high risk: A nationwide nested case-control study

Kim

Jang

Nam

et al. 2018

Journal of Hepatology

106

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“…TM4SF5 promoted SREBPs expression in fatty livers via the down-regulation of SIRT1, which deacetylates and negatively regulates SREBPs activity and expression (Agarwal & Agarwal, 2017). SREBP-1a and SREBP-1c or SREBP-2 are involved in FFA or cholesterol synthesis, respectively (Moon, 2017). SIRT1 overexpression decreased mature SREBP1 and SOCS1/3 levels.…”

Section: Discussionmentioning

confidence: 99%

Differential TM4SF5-mediated SIRT1 modulation and signaling for chronic liver disease

Ryu

Kim

Kang

et al. 2020

Preprint

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Here we show the roles of transmembrane 4 L six family member 5 (TM4SF5) in the progression of nonalcoholic steatosis (or NAFL) to steatohepatitis (NASH). The overexpression of TM4SF5 caused nonalcoholic steatosis and NASH in an age-dependent manner. Initially, TM4SF5-positive hepatocytes and livers exhibited lipid accumulation, decreased SIRT1, increased SREBPs levels, and inactive STAT3 via SOCS1/3 upregulation. In older animals, TM4SF5 under an inflammatory environment increased SIRT1 expression and STAT3 activity with no significant change to SOCSs and SREBPs levels, leading to active STAT3-mediated fibrotic extracellular matrix (ECM) production. Liver tissues from clinical human patients with NAFL or NASH also showed such a TM4SF5-SIRT1-STAT3-ECM relationship correlated with fibrosis score and age. Ligand-independent and TM4SF5-mediated STAT3 activity led to collagen I and laminins/laminin γ2 expression in hepatic stellate cells and hepatocytes, respectively. Laminin γ2 suppression abolished CCl4-mediated liver damage and ECM production and reduced SIRT1 and active-STAT3, but did not alter SREBP1 or SOCSs levels. These findings suggest that TM4SF5, CCL20, SIRT1, and/or laminin γ2 may be promising therapeutic targets against liver disease. the Tumor Microenvironment GCRC (2011-0030001) to JWL. Author contributions JR and EK performed most experiments; EK and MKK helped animal experiments; JWJ, SHN, JEK, DGS, and HJK helped with imaging experiments and with reagents; JHL, JHY, and HYK helped with clinical patient tissues; TS helped with the RNA-Seq analysis; SK helped with anti-TM4SF5 antibodies; JWL designed the experiments and wrote the manuscript. Conflict of interestsThe authors declare no competing interests. 26The paper explained PROBLEM: Nonalcoholic liver disease is a chronic disease with immuno-metabolic disorders during NAFLD progression to NASH/fibrosis, cirrhosis and cancer. The molecular mechanisms for the earlier progression to NASH/fibrosis remain unclear. RESULTS:Tm4sf5-engineered mice revealed that TM4SF5-dependent SIRT1 modulation and chemokines promoted NAFLD, NASH, and fibrosis in an age-dependent manner.TM4SF5/STAT3-mediated laminin expression in hepatocytes critically promoted the earlier progression toward NASH.

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“…SREBP-1 is activated by insulin and induces the expression of lipogenic genes 31 , increasing fatty acid synthesis from glucose 32 . However, in obese insulin-resistant subjects, the persistent hyperinsulinemia maintains lipogenesis 5-fold higher than in healthy subjects, even during fasting 33 , and leading to triglyceride accumulation 34 . In addition to hepatic lipogenesis, the increased flow of fatty acids from adipose tissue to the liver exacerbates the accumulation of triglycerides, resulting in the development of hepatic steatosis or NAFLD, which is highly prevalent in obese subjects 35 .…”

Section: Lipotoxicity As a Common Mediator In Organ Damagementioning

confidence: 98%

Nutrigenomics as a Tool in the Prevention of Lipotoxicity: The Case of Soy Protein

Torres

Torre-Villalvazo

Tovar

2019

RIC

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Obesity is associated with an increase of several metabolic disorders leading to the development of diseases such as type 2 diabetes and cardiovascular disease. This is due in part to the ectopic accumulation of triglycerides in organs that are non-adipose tissues, leading to lipotoxicity. Particularly, in the liver, the accumulation of lipids, mainly of triglycerides, leads to the formation of fatty liver. The accumulation of lipids in skeletal muscle and pancreas associates with insulin resistance and a decrease in insulin secretion, respectively. In addition, it has been suggested that dysbiosis of the gut microbiota can contribute to the process of lipid accumulation in non-adipose tissues, especially in the liver. The aim of the present review is to highlight the mechanisms associated with the development of lipotoxicity, and how with the advances in nutrigenomics, it is now possible to understand the molecular mechanisms by which some nutrients can attenuate the ectopic accumulation of triglycerides in non-adipose tissues. Particularly, we emphasize research conducted on the molecular mechanisms of action of soy protein and some of its isoflavones, and how these can reduce lipotoxicity by preventing the accumulation of lipids in the liver, skeletal muscle, and pancreas, as well as their role on the gut microbiota to attenuate the development of fatty liver. Thus, nutrigenom-ics is opening new dietary strategies based on several functional foods that can be used to ameliorate the pathologies associ

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The SCAP/SREBP Pathway: A Mediator of Hepatic Steatosis

Cited by 89 publications

References 20 publications

Statin use and the risk of hepatocellular carcinoma in patients at high risk: A nationwide nested case-control study

Statin use and the risk of hepatocellular carcinoma in patients at high risk: A nationwide nested case-control study

Differential TM4SF5-mediated SIRT1 modulation and signaling for chronic liver disease

Nutrigenomics as a Tool in the Prevention of Lipotoxicity: The Case of Soy Protein

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