Regulation of Hepatic Cholesteryl Ester Transfer Protein Expression and Reverse Cholesterol Transport by Inhibition of DNA Topoisomerase II

Li, Mengyang; Chen, Yuanli; Zhang, Ling; Wang, Qixue; Ma, Xingzhe; Li, Xiaoju; Xiang, Rong; Zhu, Yan; Qin, Shucun; Yu, Yang; Duan, Yajun; Han, Jihong

doi:10.1074/jbc.m115.643015

Cited by 8 publications

(3 citation statements)

References 39 publications

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“…Etoposide is a semisynthetic agent that binds to and inhibits topoisomerase II, preventing repair of DNA breaks. To date there are no reports of etoposide‐induced steatosis, although it does impact cholesterol metabolism through its effects on hepatic cholesteryl ester transfer protein . EPOCH‐R also differs from R‐CHOP in the delivery of doxorubicin (infusional versus bolus), which may impact hepatic toxicity, and in a higher prednisone dose, although this is unlikely to result in a delayed effect.…”

Section: Discussionmentioning

confidence: 99%

Development of Hepatic Steatosis After Chemotherapy for Non‐Hodgkin Lymphoma

et al. 2018

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Nonalcoholic fatty liver disease is the most common liver disorder in the developed world. Although typically reflecting caloric overload, it can also be secondary to drug toxicity. We aimed to describe the incidence and risk factors for de novo steatosis during chemotherapy for non‐Hodgkin lymphoma (NHL). In this retrospective case‐control study, adult patients with NHL were treated with rituximab, cyclophosphamide, doxorubicin, prednisone, and vincristine (R‐CHOP) or R‐CHOP + etoposide (EPOCH‐R). Patients with liver disease or steatosis were excluded. Abdominal computed tomography was performed pretreatment and at 3‐ to 6‐month intervals and reviewed for steatosis. Patients with de novo steatosis were matched 1:1 to controls by age, sex, and ethnicity. Of 251 treated patients (median follow‐up 53 months), 25 (10%) developed de novo steatosis, with the vast majority (23 of 25; 92%) developing it after chemotherapy. Of those, 14 (61%) developed steatosis within the first 18 months posttreatment and 20 (87%) within 36 months. Cases had higher baseline body mass index (BMI; mean ± SD, 29.0 ± 6.5 versus 26.0 ± 5.2 kg/m2; P = 0.014) and hyperlipidemia (12% versus 2%; P = 0.035). Although their weights did not change during chemotherapy, BMI in cases increased by 2.4 ± 2 kg/m2 (mean ± SD) from end of treatment to steatosis compared to 0.68 ± 1.4 in controls (P = 0.003). Etoposide‐containing regimens were associated with a shorter time to steatosis (median 34 weeks versus 154 weeks; P < 0.001) despite similar baseline risk factors. Conclusion: The recovery period from NHL chemotherapy appears to be a “hot spot” for development of fatty liver, driven by early posttreatment weight gain, especially in subjects with baseline risk factors.

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Section: Discussionmentioning

confidence: 99%

Development of Hepatic Steatosis After Chemotherapy for Non‐Hodgkin Lymphoma

et al. 2018

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“…It aids in the transportation of fat phosphate, which is a constituent of HDL particles [237]. Additionally, LXRs regulate the gene expression of cholesteryl ester transfer protein (CETP), which is accountable for the transfer of cholesterol from HDL to other lipid particles [238].…”

Section: Er Stress and Nuclear Receptors In Adipogenesismentioning

confidence: 99%

Endoplasmic Reticulum Stress and Its Impact on Adipogenesis: Molecular Mechanisms Implicated

Kim,

Lee,

et al. 2023

Nutrients

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Endoplasmic reticulum (ER) stress plays a pivotal role in adipogenesis, which encompasses the differentiation of adipocytes and lipid accumulation. Sustained ER stress has the potential to disrupt the signaling of the unfolded protein response (UPR), thereby influencing adipogenesis. This comprehensive review illuminates the molecular mechanisms that underpin the interplay between ER stress and adipogenesis. We delve into the dysregulation of UPR pathways, namely, IRE1-XBP1, PERK and ATF6 in relation to adipocyte differentiation, lipid metabolism, and tissue inflammation. Moreover, we scrutinize how ER stress impacts key adipogenic transcription factors such as proliferator-activated receptor γ (PPARγ) and CCAAT-enhancer-binding proteins (C/EBPs) along with their interaction with other signaling pathways. The cellular ramifications include alterations in lipid metabolism, dysregulation of adipokines, and aged adipose tissue inflammation. We also discuss the potential roles the molecular chaperones cyclophilin A and cyclophilin B play in adipogenesis. By shedding light on the intricate relationship between ER stress and adipogenesis, this review paves the way for devising innovative therapeutic interventions.

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“…In dyslipidaemic animals, anacetrapib increased RCT, whereas an equipotent dose of dalcetrapib reduced it. Liu et al ( 2015 ) found that inhibition of DNA topoisomerase II (Topo II) by etoposide, tenipooside or Topo II siRNA increased CETP gene expression and CETP secretion in HepG2 cells. When given to CETP transgenic mice, teniposide induced CETP expression in the liver, and increased macrophage-to-feces RCT to a greater degree than in wild-type mice with no CETP.…”

mentioning

confidence: 99%

Cholesteryl ester transfer protein: ace of spades, queen of hearts, or the joker?

Miller

2015

Front. Pharmacol.

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Regulation of Hepatic Cholesteryl Ester Transfer Protein Expression and Reverse Cholesterol Transport by Inhibition of DNA Topoisomerase II

Cited by 8 publications

References 39 publications

Development of Hepatic Steatosis After Chemotherapy for Non‐Hodgkin Lymphoma

Development of Hepatic Steatosis After Chemotherapy for Non‐Hodgkin Lymphoma

Endoplasmic Reticulum Stress and Its Impact on Adipogenesis: Molecular Mechanisms Implicated

Cholesteryl ester transfer protein: ace of spades, queen of hearts, or the joker?

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