FATP2-targeted therapies — A role beyond fatty liver disease

Qiu, Peishan; Wang, Haizhou; Zhang, Mengna; Zhang, Meng; Peng, Ruyi; Zhao, Qiu; Liu, Jing

doi:10.1016/j.phrs.2020.105228

Cited by 35 publications

(21 citation statements)

References 80 publications

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“…FATP2 might be considered as an early marker for the development of overweight disorder after a high-fat diet[ 188 ]. A high-fat diet significantly upregulated fatp2 expression in the intestine of mice[ 188 , 189 ] It has a role in hepatic long-chain fatty acid uptake[ 190 ]. Due to its important role in fatty acid transport, FATP2 can be a promising pharmacological target in diseases which are characterized by an abnormal accumulation of intracellular FAs and lipids which may eventually result in irreversible hepatic cirrhosis[ 191 , 192 ].…”

Section: Potential Therapeutic Application Targeting Acyl-coa Synthetasesmentioning

confidence: 99%

“…Both of them reduce intestinal fat absorption of 13C labeled oleate[ 186 ]. In addition to its contribution to the development of metabolic liver diseases, FATP2 promotes the growth of cancer cells and induces their resistance to targeted therapies[ 190 ]. A study by Veglia et al [ 194 ] demonstrated that lipofermata abrogated the activity of polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) and substantially delayed tumor progression in colon cancer cell line CT26 tumor-bearing mice.…”

Section: Potential Therapeutic Application Targeting Acyl-coa Synthetasesmentioning

confidence: 99%

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Fatty acid metabolism and acyl-CoA synthetases in the liver-gut axis

Ma¹,

Nenkov²,

Chen³

et al. 2021

WJH

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Fatty acids are energy substrates and cell components which participate in regulating signal transduction, transcription factor activity and secretion of bioactive lipid mediators. The acyl-CoA synthetases (ACSs) family containing 26 family members exhibits tissue-specific distribution, distinct fatty acid substrate preferences and diverse biological functions. Increasing evidence indicates that dysregulation of fatty acid metabolism in the liver-gut axis , designated as the bidirectional relationship between the gut, microbiome and liver, is closely associated with a range of human diseases including metabolic disorders, inflammatory disease and carcinoma in the gastrointestinal tract and liver. In this review, we depict the role of ACSs in fatty acid metabolism, possible molecular mechanisms through which they exert functions, and their involvement in hepatocellular and colorectal carcinoma, with particular attention paid to long-chain fatty acids and small-chain fatty acids. Additionally, the liver-gut communication and the liver and gut intersection with the microbiome as well as diseases related to microbiota imbalance in the liver-gut axis are addressed. Moreover, the development of potentially therapeutic small molecules, proteins and compounds targeting ACSs in cancer treatment is summarized.

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Section: Potential Therapeutic Application Targeting Acyl-coa Synthetasesmentioning

confidence: 99%

Section: Potential Therapeutic Application Targeting Acyl-coa Synthetasesmentioning

confidence: 99%

Fatty acid metabolism and acyl-CoA synthetases in the liver-gut axis

Ma¹,

Nenkov²,

Chen³

et al. 2021

WJH

View full text Add to dashboard Cite

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“…As opposed to the primary CRC, CD36 was found to be upregulated in the metastatic lesions of CRC, implying the higher dependency of metastatic tumors on FA uptake as compared with primary CRC [93][94][95]. Fatty acid transport proteins (FATPs), the solute carrier 27 (Slc27) family of proteins, play a role in exogenous fatty acid transport, in addition to very long-chain acyl-CoA synthetase [96,97]. FATPs transport LCFA to cells and activate LCFAs through ACSVL carrier acylation.…”

Section: Lipid Metabolismmentioning

confidence: 99%

“…FATPs transport LCFA to cells and activate LCFAs through ACSVL carrier acylation. The expression of FATP2, one family member of FATPs, was associated with increased tumor growth and therapy resistance [97].…”

Section: Lipid Metabolismmentioning

confidence: 99%

Metabolic Reprogramming of Colorectal Cancer Cells and the Microenvironment: Implication for Therapy

Nenkov

Gaßler

et al. 2021

IJMS

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Colorectal carcinoma (CRC) is one of the most frequently diagnosed carcinomas and one of the leading causes of cancer-related death worldwide. Metabolic reprogramming, a hallmark of cancer, is closely related to the initiation and progression of carcinomas, including CRC. Accumulating evidence shows that activation of oncogenic pathways and loss of tumor suppressor genes regulate the metabolic reprogramming that is mainly involved in glycolysis, glutaminolysis, one-carbon metabolism and lipid metabolism. The abnormal metabolic program provides tumor cells with abundant energy, nutrients and redox requirements to support their malignant growth and metastasis, which is accompanied by impaired metabolic flexibility in the tumor microenvironment (TME) and dysbiosis of the gut microbiota. The metabolic crosstalk between the tumor cells, the components of the TME and the intestinal microbiota further facilitates CRC cell proliferation, invasion and metastasis and leads to therapy resistance. Hence, to target the dysregulated tumor metabolism, the TME and the gut microbiota, novel preventive and therapeutic applications are required. In this review, the dysregulation of metabolic programs, molecular pathways, the TME and the intestinal microbiota in CRC is addressed. Possible therapeutic strategies, including metabolic inhibition and immune therapy in CRC, as well as modulation of the aberrant intestinal microbiota, are discussed.

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“…Based on their important roles in lipid metabolism, CD36, FATP2 and FGF21 are also considered as potential therapeutic targets for NAFLD and CKD [30,139,140]. Additionally, miRNAs might be molecular targets for metabolic regulation of NAFLD or CKD [141][142][143][144], the delivery and application of which require further investigation.…”

Section: Lipid Mediators As Optional Therapeutic Targetsmentioning

confidence: 99%

Lipid Disorders in NAFLD and Chronic Kidney Disease

et al. 2021

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Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver dysfunction and is characterized by exaggerated lipid accumulation, inflammation and even fibrosis. It has been shown that NAFLD increases the risk of other chronic diseases, particularly chronic kidney disease (CKD). Lipid in excess could lead to liver and kidney lesions and even end-stage disease through diverse pathways. Dysregulation of lipid uptake, oxidation or de novo lipogenesis contributes to the toxic effects of ectopic lipids which promotes the development and progression of NAFLD and CKD via triggering oxidative stress, apoptosis, pro-inflammatory and profibrotic responses. Importantly, dyslipidemia and release of pro-inflammatory cytokines caused by NAFLD (specifically, nonalcoholic steatohepatitis) are considered to play important roles in the pathological progression of CKD. Growing evidence of similarities between the pathogenic mechanisms of NAFLD and those of CKD has attracted attention and urged researchers to discover their common therapeutic targets. Here, we summarize the current understanding of molecular aberrations underlying the lipid metabolism of NAFLD and CKD and clinical evidence that suggests the relevance of these pathways in humans. This review also highlights the orchestrated inter-organ cross-talk in lipid disorders, as well as therapeutic options and opportunities to counteract NAFLD and CKD.

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FATP2-targeted therapies — A role beyond fatty liver disease

Cited by 35 publications

References 80 publications

Fatty acid metabolism and acyl-CoA synthetases in the liver-gut axis

Fatty acid metabolism and acyl-CoA synthetases in the liver-gut axis

Metabolic Reprogramming of Colorectal Cancer Cells and the Microenvironment: Implication for Therapy

Lipid Disorders in NAFLD and Chronic Kidney Disease

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