scholarly journals Targeting De Novo Lipogenesis and Cholesterol Biosynthesis Simultaneously is a Novel Therapeutic Option for Hepatocellular Carcinoma

2021 ◽  
Vol Volume 8 ◽  
pp. 19-21
Author(s):  
Qian Liu ◽  
Xifeng Dong
Keyword(s):  
Hepatocellular Carcinoma ◽  
De Novo ◽  
Therapeutic Option ◽  
Cholesterol Biosynthesis ◽  
De Novo Lipogenesis ◽  
Novel Therapeutic

Raman spectroscopic imaging for investigations of de novo lipogenesis in hepatocellular carcinoma

2014 ◽  
Vol 52 (08) ◽  
Author(s):  
T Tolstik ◽  
C Marquardt ◽  
C Matthäus ◽  
C Beleites ◽  
C Krafft ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
De Novo ◽  
Spectroscopic Imaging ◽  
De Novo Lipogenesis ◽  
Raman Spectroscopic

Regulation of the SREBP transcription factors by mTORC1

2011 ◽  
Vol 39 (2) ◽  
pp. 495-499 ◽  
Author(s):  
Caroline A. Lewis ◽  
Beatrice Griffiths ◽  
Claudio R. Santos ◽  
Mario Pende ◽  
Almut Schulze
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Synthase ◽  
Target Genes ◽  
De Novo ◽  
Regulatory Element ◽  
Cholesterol Biosynthesis ◽  
Mammalian Target Of Rapamycin ◽  
Lipid Biosynthesis ◽  
De Novo Lipogenesis ◽  
Genes Encoding

In recent years several reports have linked mTORC1 (mammalian target of rapamycin complex 1) to lipogenesis via the SREBPs (sterol-regulatory-element-binding proteins). SREBPs regulate the expression of genes encoding enzymes required for fatty acid and cholesterol biosynthesis. Lipid metabolism is perturbed in some diseases and SREBP target genes, such as FASN (fatty acid synthase), have been shown to be up-regulated in some cancers. We have previously shown that mTORC1 plays a role in SREBP activation and Akt/PKB (protein kinase B)-dependent de novo lipogenesis. Our findings suggest that mTORC1 plays a crucial role in the activation of SREBP and that the activation of lipid biosynthesis through the induction of SREBP could be part of a regulatory pathway that co-ordinates protein and lipid biosynthesis during cell growth. In the present paper, we discuss the increasing amount of data supporting the potential mechanisms of mTORC1-dependent activation of SREBP as well as the implications of this signalling pathway in cancer.

scholarly journals De novo lipogenesis is elicited dramatically in human hepatocellular carcinoma especially in hepatitis C virus‐induced hepatocellular carcinoma

MedComm ◽  
2020 ◽  
Vol 1 (2) ◽  
pp. 178-187
Author(s):  
Shaojian Li ◽  
Ruonan Liu ◽  
Qinling Pan ◽  
Genshu Wang ◽  
Daorou Cheng ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
De Novo ◽  
Human Hepatocellular Carcinoma ◽  
De Novo Lipogenesis

ZHX2 inhibits SREBP1c ‐mediated de novo lipogenesis in hepatocellular carcinoma via miR ‐24‐3p

2020 ◽  
Vol 252 (4) ◽  
pp. 358-370
Author(s):  
Xiangguo Yu ◽  
Qinghai Lin ◽  
Zhuanchang Wu ◽  
Yankun Zhang ◽  
Tixiao Wang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
De Novo ◽  
De Novo Lipogenesis

scholarly journals Regular exercise potentiates energetically expensive hepatic de novo lipogenesis during early weight regain

2019 ◽  
Vol 317 (5) ◽  
pp. R684-R695
Author(s):  
David M. Presby ◽  
L. Allyson Checkley ◽  
Matthew R. Jackman ◽  
Janine A. Higgins ◽  
Kenneth L. Jones ◽  
...  
Keyword(s):  
Weight Loss ◽  
Energy Expenditure ◽  
De Novo ◽  
Energy Gap ◽  
Cholesterol Biosynthesis ◽  
Density Lipoprotein ◽  
De Novo Lipogenesis ◽  
Positive Energy ◽  
Hepatic Expression ◽  
Expression Of Genes

Exercise is a potent facilitator of long-term weight loss maintenance (WLM), whereby it decreases appetite and increases energy expenditure beyond the cost of the exercise bout. We have previously shown that exercise may amplify energy expenditure through energetically expensive nutrient deposition. Therefore, we investigated the effect of exercise on hepatic de novo lipogenesis (DNL) during WLM and relapse to obesity. Obese rats were calorically restricted with (EX) or without (SED) treadmill exercise (1 h/day, 6 days/wk, 15 m/min) to induce and maintain weight loss. After 6 wk of WLM, subsets of WLM-SED and WLM-EX rats were allowed ad libitum access to food for 1 day to promote relapse (REL). An energy gap-matched group of sedentary, relapsing rats (REL-GM) were provided a diet matched to the positive energy imbalance of the REL-EX rats. During relapse, exercise increased enrichment of hepatic DN-derived lipids and induced hepatic molecular adaptations favoring DNL compared with the gap-matched controls. In the liver, compared with both REL-SED and REL-GM rats, REL-EX rats had lower hepatic expression of genes required for cholesterol biosynthesis; greater hepatic expression of genes that mediate very low-density lipoprotein synthesis and secretion; and greater mRNA expression of Cyp27a1, which encodes an enzyme involved in the biosynthesis of bile acids. Altogether, these data provide compelling evidence that the liver has an active role in exercise-mediated potentiation of energy expenditure during early relapse.

scholarly journals Role of hepatoma‐derived growth factor in promoting de novo lipogenesis and tumorigenesis in hepatocellular carcinoma

2018 ◽  
Vol 12 (9) ◽  
pp. 1480-1497 ◽  
Author(s):  
Xuejie Min ◽  
Jun Wen ◽  
Li Zhao ◽  
Kaiying Wang ◽  
Qingli Li ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Growth Factor ◽  
De Novo ◽  
De Novo Lipogenesis

scholarly journals Cholesterol biosynthesis supports the growth of hepatocarcinoma lesions depleted of fatty acid synthase in mice and humans

Gut ◽  
2019 ◽  
Vol 69 (1) ◽  
pp. 177-186 ◽  
Author(s):  
Li Che ◽  
Wenna Chi ◽  
Yu Qiao ◽  
Jie Zhang ◽  
Xinhua Song ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Cell Lines ◽  
Knockout Mice ◽  
Fatty Acid Synthase ◽  
De Novo ◽  
Therapeutic Option ◽  
Regulatory Element ◽  
Cholesterol Biosynthesis ◽  
Dominant Negative ◽  
Comparative Genomic

ObjectiveIncreased de novo fatty acid (FA) synthesis and cholesterol biosynthesis have been independently described in many tumour types, including hepatocellular carcinoma (HCC).DesignWe investigated the functional contribution of fatty acid synthase (Fasn)-mediated de novo FA synthesis in a murine HCC model induced by loss of Pten and overexpression of c-Met (sgPten/c-Met) using liver-specificFasnknockout mice. Expression arrays and lipidomic analysis were performed to characterise the global gene expression and lipid profiles, respectively, of sgPten/c-Met HCC from wild-type andFasnknockout mice. Human HCC cell lines were used for in vitro studies.ResultsAblation ofFasnsignificantly delayed sgPten/c-Met-driven hepatocarcinogenesis in mice. However, eventually, HCC emerged inFasnknockout mice. Comparative genomic and lipidomic analyses revealed the upregulation of genes involved in cholesterol biosynthesis, as well as decreased triglyceride levels and increased cholesterol esters, in HCC from these mice. Mechanistically, loss ofFasnpromoted nuclear localisation and activation of sterol regulatory element binding protein 2 (Srebp2), which triggered cholesterogenesis. Blocking cholesterol synthesis via the dominant negative form of Srebp2 (dnSrebp2) completely prevented sgPten/c-Met-driven hepatocarcinogenesis inFasnknockout mice. Similarly, silencing ofFASNresulted in increasedSREBP2activation and hydroxy-3-methyl-glutaryl-CoA (HMG-CoA) reductase (HMGCR)expression in human HCC cell lines. Concomitant inhibition of FASN-mediated FA synthesis and HMGCR-driven cholesterol production was highly detrimental for HCC cell growth in culture.ConclusionOur study uncovers a novel functional crosstalk between aberrant lipogenesis and cholesterol biosynthesis pathways in hepatocarcinogenesis, whose concomitant inhibition might represent a therapeutic option for HCC.

Inhibition of the oncoprotein FUBP1 by SN-38 represents a novel therapeutic option for the treatment of hepatocellular carcinoma

2016 ◽  
Vol 69 ◽  
pp. S18
Author(s):  
S. Hauck ◽  
S. Khageh Hosseini ◽  
J. Wesely ◽  
J. Trojan ◽  
K. Gerlach ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Therapeutic Option ◽  
Novel Therapeutic

scholarly journals Loss of Acot12 contributes to NAFLD independent of lipolysis of adipose tissue

2021 ◽  
Author(s):  
Sujeong Park ◽  
Jinsoo Song ◽  
In-Jeoung Baek ◽  
Kyu Yun Jang ◽  
Chang Yeob Han ◽  
...  
Keyword(s):  
De Novo ◽  
Interaction Analysis ◽  
Cholesterol Biosynthesis ◽  
De Novo Lipogenesis ◽  
Cholesterol Trafficking ◽  
Acetyl Coa ◽  
Nonalcoholic Fatty Liver ◽  
Vacuolar Protein ◽  
Specific Deletion ◽  
Stimulation Of

AbstractIn this study, we hypothesized that deregulation in the maintenance of the pool of coenzyme A (CoA) may play a crucial role in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). Specific deletion of Acot12 (Acot12−/−), the major acyl-CoA thioesterase, induced the accumulation of acetyl-CoA and resulted in the stimulation of de novo lipogenesis (DNL) and cholesterol biosynthesis in the liver. KEGG pathway analysis suggested PPARα signaling as the most significantly enriched pathway in Acot12−/− livers. Surprisingly, the exposure of Acot12−/− hepatocytes to fenofibrate significantly increased the accumulation of acetyl-CoA and resulted in the stimulation of cholesterol biosynthesis and DNL. Interaction analysis, including proximity-dependent biotin identification (BioID) analysis, suggested that ACOT12 may directly interact with vacuolar protein sorting-associated protein 33A (VPS33A) and play a role in vesicle-mediated cholesterol trafficking and the process of lysosomal degradation of cholesterol in hepatocytes. In summary, in this study, we found that ACOT12 deficiency is responsible for the pathogenesis of NAFLD through the accumulation of acetyl-CoA and the stimulation of DNL and cholesterol via activation of PPARα and inhibition of cholesterol trafficking.

scholarly journals Hormonally Induced Hepatocellular Carcinoma in Diabetic Wild Type and Carbohydrate Responsive Element Binding Protein Knockout Mice

Cells ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 2787
Author(s):  
Vincent Nuernberger ◽  
Sharif Mortoga ◽  
Christoph Metzendorf ◽  
Christian Burkert ◽  
Katrina Ehricke ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Islet Transplantation ◽  
Pancreatic Islet ◽  
De Novo ◽  
De Novo Lipogenesis ◽  
Wild Type ◽  
Pancreatic Islet Transplantation ◽  
Hepatocellular Carcinomas ◽  
Element Binding Protein ◽  
Transplantation Model

Objective: In the rat, the pancreatic islet transplantation model is an established method to induce hepatocellular carcinomas (HCC), due to insulin-mediated metabolic and molecular alterations like increased glycolysis and de novo lipogenesis and the oncogenic AKT/mTOR pathway including upregulation of the transcription factor Carbohydrate-response element-binding protein (ChREBP). ChREBP could therefore represent an essential oncogenic co-factor during hormonally induced hepatocarcinogenesis. Methods: Pancreatic islet transplantation was implemented in diabetic C57Bl/6J (wild type, WT) and ChREBP-knockout (KO) mice for 6 and 12 months. Liver tissue was examined using histology, immunohistochemistry, electron microscopy and Western blot analysis. Finally, we performed NGS-based transcriptome analysis between WT and KO liver tumor tissues. Results: Three hepatocellular carcinomas were detectable after 6 and 12 months in diabetic transplanted WT mice, but only one in a KO mouse after 12 months. Pre-neoplastic clear cell foci (CCF) were also present in liver acini downstream of the islets in WT and KO mice. In KO tumors, glycolysis, de novo lipogenesis and AKT/mTOR signalling were strongly downregulated compared to WT lesions. Extrafocal liver tissue of diabetic, transplanted KO mice revealed less glycogen storage and proliferative activity than WT mice. From transcriptome analysis, we identified a set of transcripts pertaining to metabolic, oncogenic and immunogenic pathways that are differentially expressed between tumors of WT and KO mice. Of 315 metabolism-associated genes, we observed 199 genes that displayed upregulation in the tumor of WT mice, whereas 116 transcripts showed their downregulated expression in KO mice tumor. Conclusions: The pancreatic islet transplantation model is a suitable method to study hormonally induced hepatocarcinogenesis also in mice, allowing combination with gene knockout models. Our data indicate that deletion of ChREBP delays insulin-induced hepatocarcinogenesis, suggesting a combined oncogenic and lipogenic function of ChREBP along AKT/mTOR-mediated proliferation of hepatocytes and induction of hepatocellular carcinoma.

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