Acetyl-CoA Carboxylases and Diseases

Wang, Yu; Yu, Weixing; Li, Sha; Guo, Dingyuan; He, Jie; Wang, Yugang

doi:10.3389/fonc.2022.836058

Cited by 74 publications

(66 citation statements)

References 118 publications

(158 reference statements)

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“…Except uptake of circulating FAs, DNL enables liver to synthesize FAs by using non-lipid precursors (such as sugars and proteins) [31]. The production of acetyl-CoA initially provides the substrate required for DNL, which is converted to malonyl-CoA by acetyl-CoA carboxylase (ACC) and malonyl-CoA is then converted to palmitate by fatty acid synthase (FASN) [32]. The transcriptional regulation of DNL is mainly regulated by two transcription factors: sterol regulatory elementbinding protein 1c (SREBP1c) and carbohydrate regulatory element-binding protein (ChREBP), which both stimulated by the activation of LXR and by nuclear translocation to activate target gene transcription [33,34].…”

Section: Fas and Triacylglycerol Synthesis 31 De Novo Lipogenesismentioning

confidence: 99%

Hepatic Lipid Homeostasis in NAFLD

Zhang¹,

Jia²,

Yang³

et al. 2023

Non-Alcoholic Fatty Liver Disease - New Insight and Glance Into Disease Pathogenesis

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Non-alcoholic fatty liver disease (NAFLD) is currently the most common liver disease, affecting 25% of world population. Hepatic steatosis has 60–90% prevalence among obese patients. It is also associated with multitude of detrimental effects and increased mortality. This narrative chapter investigates hepatic lipid homeostasis in NAFLD, focusing on the four molecular pathways of hepatic steatosis to lipid homeostasis in the liver. Hepatic steatosis is a consequence of lipid acquisition pathways exceeding lipid disposal pathways. In NAFLD, hepatic uptake of fatty acids and de novo lipogenesis surpass fatty acid oxidation and lipid export. The imbalance of the hepatic lipid may promote cellular damage by inducing oxidative stress in peroxisomes and cytochromes, especially with compromised mitochondrial function. Lipid export may even decrease with disease progression, sustaining the accumulation of lipids. NAFLD has a complex molecular mechanism regulating hepatic lipid homeostasis. Thus, as well as inter-individual differences, any intervention targeting one or more pathway is likely to have consequences on multiple cellular signaling pathways. We should be taken into careful consideration when developing future treatment options for NAFLD.

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Section: Fas and Triacylglycerol Synthesis 31 De Novo Lipogenesismentioning

confidence: 99%

Hepatic Lipid Homeostasis in NAFLD

Zhang¹,

Jia²,

Yang³

et al. 2023

Non-Alcoholic Fatty Liver Disease - New Insight and Glance Into Disease Pathogenesis

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“…ACC1 is localized in the cytoplasm and is the first rate-limiting enzyme in the de novo fatty acid synthesis pathway. ACC2 localizes to the mitochondrial outer membrane, produces malonyl-CoA, and regulates the activity of CPT1 involved in fatty acid β-oxidation ( 115 ). Increased activation of ACC is ordinary in human gastric cancer.…”

Section: The Function Of Lipid Metabolism Related Enzymesmentioning

confidence: 99%

The Role of Lipid Metabolism in Gastric Cancer

Cui

Zhu

et al. 2022

Front. Oncol.

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Gastric cancer has been one of the most common cancers worldwide with extensive metastasis and high mortality. Chemotherapy has been found as a main treatment for metastatic gastric cancer, whereas drug resistance limits the effectiveness of chemotherapy and leads to treatment failure. Chemotherapy resistance in gastric cancer has a complex and multifactorial mechanism, among which lipid metabolism plays a vital role. Increased synthesis of new lipids or uptake of exogenous lipids can facilitate the rapid growth of cancer cells and tumor formation. Lipids form the structural basis of biofilms while serving as signal molecules and energy sources. It is noteworthy that lipid metabolism is capable of inducing drug resistance in gastric cancer cells by reshaping the tumor micro-environment. In this study, new mechanisms of lipid metabolism in gastric cancer and the metabolic pathways correlated with chemotherapy resistance are reviewed. In particular, we discuss the effects of lipid metabolism on autophagy, biomarkers treatment and drug resistance in gastric cancer from the perspective of lipid metabolism. In brief, new insights can be gained into the development of promising therapies through an in-depth investigation of the mechanism of lipid metabolism reprogramming and resensitization to chemotherapy in gastric cancer cells, and scientific treatment can be provided by applying lipid-key enzyme inhibitors as cancer chemical sensitizers in clinical settings.

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“…As a key metabolic substrate for fatty acid synthesis, acetyl-CoA is mainly converted from mitochondria-derived citrate through the action of ATP citrate lyase (ACLY) ( Wei et al, 2020 ). The rate-limiting step in fatty acid synthesis is the synthesis of malonyl-CoA from acetyl-CoA by acetyl-CoA carboxylase (ACC) ( Wang et al, 2022 ). Then malonyl-CoA and acetyl-CoA are catalyzed and condensed by fatty acid synthase (FASN) to form 16-carbon fatty acid palmitate.…”

Section: Molecular Mechanisms Of Ferroptosismentioning

confidence: 99%

Emerging role of ferroptosis in glioblastoma: Therapeutic opportunities and challenges

Zhuo

Chen

et al. 2022

Front. Mol. Biosci.

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Glioblastoma (GBM) is the most common malignant craniocerebral tumor. The treatment of this cancer is difficult due to its high heterogeneity and immunosuppressive microenvironment. Ferroptosis is a newly found non-apoptotic regulatory cell death process that plays a vital role in a variety of brain diseases, including cerebral hemorrhage, neurodegenerative diseases, and primary or metastatic brain tumors. Recent studies have shown that targeting ferroptosis can be an effective strategy to overcome resistance to tumor therapy and immune escape mechanisms. This suggests that combining ferroptosis-based therapies with other treatments may be an effective strategy to improve the treatment of GBM. Here, we critically reviewed existing studies on the effect of ferroptosis on GBM therapies such as chemotherapy, radiotherapy, immunotherapy, and targeted therapy. In particular, this review discussed the potential of ferroptosis inducers to reverse drug resistance and enhance the sensitivity of conventional cancer therapy in combination with ferroptosis. Finally, we highlighted the therapeutic opportunities and challenges facing the clinical application of ferroptosis-based therapies in GBM. The data generated here provide new insights and directions for future research on the significance of ferroptosis-based therapies in GBM.

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Acetyl-CoA Carboxylases and Diseases

Cited by 74 publications

References 118 publications

Hepatic Lipid Homeostasis in NAFLD

Hepatic Lipid Homeostasis in NAFLD

The Role of Lipid Metabolism in Gastric Cancer

Emerging role of ferroptosis in glioblastoma: Therapeutic opportunities and challenges

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