Acetyl-CoA carboxylase (ACC) as a therapeutic target for metabolic syndrome and recent developments in ACC1/2 inhibitors

Chen, Leyuan; Duan, Yuqing; Wei, Huiqiang; Ning, Hongxin; Bi, Changfen; Zhao, Ying; Qin, Yong; Li, Yiliang

doi:10.1080/13543784.2019.1657825

Cited by 104 publications

(86 citation statements)

References 102 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Hence, new biomarkers need to be developed for the diagnosis of prostate cancer in the early stage. Many studies have indicated that ACACA is a potential target for cancer treatment 15 - 21 . Brusselmans et al found that the knockdown of ACACA resulted in a decrease in FAS, inhibition of proliferation, and induction of apoptosis in LNCaP prostate cancer cells.…”

Section: Discussionmentioning

confidence: 99%

“…Besides, it promoted glucose-mediated fatty acid synthesis, thus improving the survival rate of mice and patients with hepatocellular carcinoma 20 . ACACA decreased the synthesis of fatty acids and could be used as a therapeutic target in metabolic syndrome 21 . Studies have shown that silencing the ACACA gene may result in the inhibition of cell proliferation and induction of apoptosis in highly lipogenic prostate cancer LNCaP cells 22 .…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Down-regulation of ACACA suppresses the malignant progression of Prostate Cancer through inhibiting mitochondrial potential

Zhang¹,

Liu²,

Cai³

et al. 2021

J. Cancer

View full text Add to dashboard Cite

Background and aim: Silencing the expression of ACACA inhibits cell proliferation and induces apoptosis in prostate cancer LNCaP cells. However, the role of ACACA in other prostate cancer cells is not fully understood. Also, the effect of knocking down ACACA gene on mitochondria remains unclear. This study aimed to discover the specific role of ACACA gene in prostate cancer (PCa) DU145 and PC3 cells as well as its effects on mitochondrial potential. Methods: The expression of ACACA gene was detected in human prostate cancer tissue microarrays and assessed in different clinical stages. Then, prostate cancer cell lines with low expression of ACACA were constructed to evaluate the changes in their cell cycle, proliferation, and metabolites. The effect of ACACA on tumor formation in vivo was analyzed. Also, mito-ATP production, mitochondrial staining, and mtDNA, nicotinamide adenine dinucleotide (NAD+/NADH), and reactive oxygen species (ROS) levels were detected. Results: ACACA was expressed more strongly in prostate cancer tissues. The expression level of ACACA was higher in patients with advanced PCa than in patients with lower grades. The proliferation ability reduced in ACACA-knockdown cells. In in vivo tests, the tumor volume and weight were lower in the experimental group than in the control group. Mito-ATP production decreased significantly after ACACA suppression, mtDNA levels and MitoTracker staining decreased in the experimental group. The ratio of NAD+/NADH and ROS levels were upregulated in the experimental group. Conclusion: Targeting ACACA gene and mitochondria might serve as a novel therapy for prostate cancer treatment.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Down-regulation of ACACA suppresses the malignant progression of Prostate Cancer through inhibiting mitochondrial potential

Zhang¹,

Liu²,

Cai³

et al. 2021

J. Cancer

View full text Add to dashboard Cite

show abstract

“…Increased de novo fatty acid (FA) synthesis has been observed in many different types of cancer and is currently thought to be the major metabolic pathway exploited by cancer cells for FA acquisition 36 . To date, increased expressions of key regulators of lipogenesis, including SREBPs, acetyl-CoA carboxylase (ACC), fatty acid synthase (FASN), and stearoyl-CoA desaturase 1 (SCD1) have been observed in various human cancers 1,9,10,15,35 . Previous studies in OC also have demonstrated the up-regulation of FASN and its involvement in tumor growth and metastasis 37 .…”

Section: Discussionmentioning

confidence: 99%

“…Increased fatty acid synthesis and cholesterol biosynthesis, as well as fatty acid oxidation are supported by enhanced expression of the enzymes belonging to these pathways, which are transcriptionally regulated by the sterol regulatory element-binding protein 1 (SREBP1), sterol regulatory element-binding protein 2 (SREBP2) and peroxisome proliferator-activated receptors (PPARs), respectively 7,8 . To date, increased expressions of many enzymes involved in fatty acid synthesis and cholesterol biosynthesis, such as acetyl-CoA carboxylase (ACC) 9 , fatty acid synthase (FASN) 1 and stearoyl-CoA desaturase1 (SCD1) 10 , 3-hydroxy-3-methyl-glutarylcoenzyme A reductase (HMGCR) 11 , 3-Hydroxy-3-methylglutaryl coenzyme A (CoA) synthase (HMGCS) 12 , have been observed in many different types of cancer. As major transcription factors that control the expression of enzymes involved in fatty acid and cholesterol biosynthesis, increased expressions and transcriptional activities of SREBP1 and SREBP2, which contributed to tumor progression, have also been demonstrated in several cancer types [13][14][15] .…”

Section: Introductionmentioning

confidence: 99%

MIEF2 reprograms lipid metabolism to drive progression of ovarian cancer through ROS/AKT/mTOR signaling pathway

Zhao

Shi

et al. 2021

Cell Death Dis

View full text Add to dashboard Cite

MIEF2 (mitochondrial elongation factor 2) is one of the key regulators of mitochondrial fission. Bioinformatics analysis indicated that high expression of MIEF2 predicted a poor prognosis in ovarian cancer patients. However, the relationship between MIEF2 and aberrant lipid metabolism in OC remains elusive. In this study, we demonstrated that MIEF2 significantly promoted lipid synthesis, while has no significant effect on fatty acid uptake and oxidation in OC cells. MIEF2 enhanced de novo fatty acid synthesis through up-regulating the expression of sterol regulatory element binding protein 1 (SREBP1) and its transcriptional target lipogenic genes ACC1, FASN and SCD1. Meanwhile, MIEF2-promoted cholesterol biosynthesis through up-regulating the expression of sterol regulatory element binding protein 2 (SREBP2) and its transcriptional target cholesterol biosynthesis genes HMGCS1 and HMGCR. Mechanistically, increased mitochondrial reactive oxygen species (ROS) production and subsequently activation of AKT/mTOR signaling pathway was found to be involved in the up-regulation of SREBP1 and SREBP2 in OC cells. Moreover, cell growth and metastasis assays indicated that MIEF2-regulated fatty acid synthesis and cholesterol biosynthesis played a critical role in the progression of OC. Taken together, our findings indicate that MIEF2 is a critical regulator of lipid synthesis in OC, which provides a strong line of evidence for this molecule to serve as a drug target in the treatment of this malignancy.

show abstract

“…In addition, lipid synthesis inhibition is a strategy to fight microbial infections that are known to take advantage of cell lipid storage, and ACACA inhibitors have been designed to develop antimicrobial strategies in infectious diseases [ 79 ].…”

Section: Discussionmentioning

confidence: 99%

Cystic Fibrosis Defective Response to Infection Involves Autophagy and Lipid Metabolism

Mingione

Ottaviano

Barcella

et al. 2020

Cells

View full text Add to dashboard Cite

Cystic fibrosis (CF) is a hereditary disease, with 70% of patients developing a proteinopathy related to the deletion of phenylalanine 508. CF is associated with multiple organ dysfunction, chronic inflammation, and recurrent lung infections. CF is characterized by defective autophagy, lipid metabolism, and immune response. Intracellular lipid accumulation favors microbial infection, and autophagy deficiency impairs internalized pathogen clearance. Myriocin, an inhibitor of sphingolipid synthesis, significantly reduces inflammation, promotes microbial clearance in the lungs, and induces autophagy and lipid oxidation. RNA-seq was performed in Aspergillusfumigatus-infected and myriocin-treated CF patients’ derived monocytes and in a CF bronchial epithelial cell line. Fungal clearance was also evaluated in CF monocytes. Myriocin enhanced CF patients’ monocytes killing of A. fumigatus. CF patients’ monocytes and cell line responded to infection with a profound transcriptional change; myriocin regulates genes that are involved in inflammation, autophagy, lipid storage, and metabolism, including histones and heat shock proteins whose activity is related to the response to infection. We conclude that the regulation of sphingolipid synthesis induces a metabolism drift by promoting autophagy and lipid consumption. This process is driven by a transcriptional program that corrects part of the differences between CF and control samples, therefore ameliorating the infection response and pathogen clearance in the CF cell line and in CF peripheral blood monocytes.

show abstract

Acetyl-CoA carboxylase (ACC) as a therapeutic target for metabolic syndrome and recent developments in ACC1/2 inhibitors

Cited by 104 publications

References 102 publications

Down-regulation of ACACA suppresses the malignant progression of Prostate Cancer through inhibiting mitochondrial potential

Down-regulation of ACACA suppresses the malignant progression of Prostate Cancer through inhibiting mitochondrial potential

MIEF2 reprograms lipid metabolism to drive progression of ovarian cancer through ROS/AKT/mTOR signaling pathway

Cystic Fibrosis Defective Response to Infection Involves Autophagy and Lipid Metabolism

Contact Info

Product

Resources

About