Hepatic Slug epigenetically promotes liver lipogenesis, fatty liver disease, and type 2 diabetes

Liu, Yan; Lin, Haiyan; Jiang, Lin; Shang, Qingsen; Yin, Lei; Lin, Jiandie D.; Wu, Weixin; Rui, Liangyou

doi:10.1172/jci128073

Cited by 35 publications

(38 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…There is convincing evidence, however, indicating that the regulation of CD36 expression is not largely linked to the HIF1α/SREBP1c signaling pathway in hepatocytes. Notably, it has been recently reported that hepatocyte-specific Srebp1 downregulation did not affect expression of genes involved in FFA uptake as Cd36 in mouse livers (30). In addition, we have just demonstrated that both CD36 expression and triglyceride content increased in mouse and human liver cells under hypoxic conditions and that silencing HIF2A gene markedly suppressed both CD36 gene upregulation and lipid accumulation in hepatocytes (14).…”

Section: Discussionsupporting

confidence: 46%

Intrahepatic Expression of Fatty Acid Translocase CD36 Is Increased in Obstructive Sleep Apnea

et al. 2020

View full text Add to dashboard Cite

Nocturnal intermittent hypoxia (IH) featuring obstructive sleep apnea (OSA) dysregulates hepatic lipid metabolism and might contribute to the development of non-alcoholic fatty liver disease (NAFLD) observed in OSA patients. However, further research is required to better understanding the molecular mechanisms underlying IH-induced hepatic lipid accumulation. Therefore, the aim of the present study was to determine the effects of OSA on hepatic CD36 expression and the impact of IH by using a mouse model of OSA. Histological analysis, lipid content and CD36 expression were assessed in livers from subjects who underwent liver biopsy and polygraphic study during sleep, and in livers from mice submitted to chronic IH mimicking OSA. Among those who presented OSA features, NAFLD were significantly more frequent than in control subjects with normal respiratory function (77.8 vs. 36.4%, respectively), and showed more severe liver disease. Interestingly, CD36 expression was significantly overexpressed within the liver of OSA patients with respect to controls, and a significant positive correlation was observed between hepatic levels of CD36 and the values of two well-known respiratory parameters that characterized OSA: apnea/hypopnea index (AHI) and oxygen desaturation index (ODI). Moreover, hepatic lipid accumulation as well as induction of hepatic lipogenic genes, and CD36 mRNA and protein expression were significantly higher in livers from mice exposed to IH conditions for 8 weeks than in their corresponding littermates. This study provides novel evidence that IH featuring OSA could contribute to NAFLD setup partly by upregulating hepatic CD36 expression.

show abstract

Section: Discussionsupporting

confidence: 46%

Intrahepatic Expression of Fatty Acid Translocase CD36 Is Increased in Obstructive Sleep Apnea

et al. 2020

View full text Add to dashboard Cite

show abstract

“…18 Additionally, hyperinsulinemia may affect histone modification and contribute to the development of HCC through the altered expression of genes involved in cellular signaling. 19 These epigenetic alterations can lead to the dysregulation of adipokine secretion and activation of PI3K/Akt, JAK/STAT, NF-κB, mTOR, trans-4-hydroxy-2-nonenal, and the nuclear factor In summary, obesity is a major cause of inflammation in adipose tissue as well as the liver; additionally, it can induce insulin resistance, as well as affect the immune systems in the gut and liver. Some reports show immunological aspects of metabolic disease-related HCC and its treatment.…”

mentioning

confidence: 99%

“…For example, glycine N-methyltransferase knockout mice, which develop NASH and HCC, show hypermethylation on the promoter of the tumor suppressor Ras-association domain family member 1, suppression of the cytokine signaling 2 gene, and activation of the Ras and JAK/STAT signaling pathway [ 18 ]. Additionally, hyperinsulinemia may affect histone modification and contribute to the development of HCC through the altered expression of genes involved in cellular signaling [ 19 ]. These epigenetic alterations can lead to the dysregulation of adipokine secretion and activation of PI3K/Akt, JAK/STAT, NF-κB, mTOR, trans-4-hydroxy-2-nonenal, and the nuclear factor erythroid 2-related factor 1 oncogenic pathway in hepatocytes.…”

mentioning

confidence: 99%

Metabolic disease as a risk of hepatocellular carcinoma

Nishida

2021

Clin Mol Hepatol

View full text Add to dashboard Cite

“…Slug expression in mouse liver was sufficient to induce liver triglyceride accumulation, whereas chronic or acute hepatocyte Slug knockout decreased liver triglycerides in both sexes. These phenotypes were associated with concomitant changes in the mRNA and protein expression of de novo lipogenesis enzymes, especially Fasn (7).…”

Section: Epigenetic Regulation Of Lipogenesismentioning

confidence: 99%

“…Despite these known transcription factormediated pathways, the epigenetic regulation of lipogenesis -and its ability to medi-ate insulin-stimulated lipogenesis -is less well understood. In this issue of the JCI, Yan Liu, Haiyan Lin, and colleagues demonstrate a unique role for the transcription factor Slug (also known as Snai2 or Snail2) in the epigenetic activation of lipogenic gene expression, downstream of hepatic insulin signaling (7).…”

Section: Epigenetic Regulation Of Lipogenesismentioning

confidence: 99%