Progress of SLC13A5 as a potential pharmacological target of metabolic diseases

NIU Qun; SUN Qiushuang; QIU Zhixia; HUANG Fang

doi:10.11665/j.issn.1000-5048.20200513

Journal of China Pharmaceutical University > 2020 > 51(5): 607-613. > DOI: 10.11665/j.issn.1000-5048.20200513

NIU Qun, SUN Qiushuang, QIU Zhixia, HUANG Fang. Progress of SLC13A5 as a potential pharmacological target of metabolic diseases[J]. Journal of China Pharmaceutical University, 2020, 51(5): 607-613. DOI: 10.11665/j.issn.1000-5048.20200513

Citation:

PDF (939 KB)

Progress of SLC13A5 as a potential pharmacological target of metabolic diseases

More Information

Received Date: February 22, 2020
Revised Date: September 14, 2020

Graphical Abstract

Abstract

Abstract

The solute carrier (SLC) consists of more than 400 transport proteins mediating the influx and efflux of ions, nucleotides, sugars and other exogenous and endogenous substances across biological membranes. Over 80 SLC carrier proteins have been reported to be closely associated with human diseases, in which more than 30 SLC proteins have been regarded as the potential drug targets. SLC13A5 mediates transmembrane transport of substances such as citrate, which is connected with de novo lipid synthesis (DNL). Studies have found that SLC13A5 is related to metabolic diseases such as obesity, insulin resistance (IR), non-alcoholic fatty liver disease (NAFLD). At present, there is no specific drug for clinical treatment of metabolic diseases caused by lipid metabolism disorders, especially NAFLD. Therefore, this paper summarizes the effect of SLC13A5 on metabolic regulation and its potential as a pharmacological target for metabolic diseases treatment, aiming to provide a reference for the research and development of drugs related to metabolic diseases.
- SLC13A5,
- citrate,
- obesity,
- non-alcoholic fatty liver disease,
- insulin resistance,
- metabolic diseases

FullText(HTML)

References (35)

References

[1]	. Am J Hum Biol，2012，24（2）：101?106.
[2]	von Loeffelholz C，Lieske S，Neusch?fer-Rube F，et al. The human longevity gene homolog INDY and interleukin-6 interact in hepatic lipid metabolism［J］. Hepatology，2017，66（2）：616?630.
[3]	Birkenfeld AL，Lee HY，Guebre-Egziabher F，et al. Deletion of the mammalian INDY homolog mimics aspects of dietary restriction and protects against adiposity and insulin resistance in mice［J］. Cell Metab，2011，14（2）：184?195.
[4]	Huard K，Brown J，Jones JC，et al. Discovery and characterization of novel inhibitors of the sodium-coupled citrate transporter （NaCT or SLC13A5）［J］. Sci Rep，2015，5：17391.
[5]	Willmes DM，Birkenfeld AL. The role of INDY in metabolic regulation［J］. Comput Struct Biotechnol J，2013，6：e201303020.
[6]	Lee S，Kesby JP，Muslim MD，et al. Hyperserotonaemia and reduced brain serotonin levels in NaS1 sulphate transporter null mice［J］. Neuroreport，2007，18（18）：1981?1985.
[7]	Lee S，Dawson PA，Hewavitharana AK，et al. Disruption of NaS1 sulfate transport function in mice leads to enhanced acetaminophen-induced hepatotoxicity［J］. Hepatology，2006，43（6）：1241?1247.
[8]	Dawson PA，Richard K，Perkins A，et al. Nutrient sulfate supply from mother to fetus：placental adaptive responses during human and animal gestation［J］. Placenta，2017，54：45?51.
[9]	Barnes SK，Eiby YA，Lee S，et al. Structure，organization and tissue expression of the pig SLC13A1 and SLC13A4 sulfate transporter genes［J］. Biochem Biophys Rep，2017，10：215?223.
[10]	Hamm LL，Hering-Smith KS. Pathophysiology of hypocitraturic nephrolithiasis［J］. Endocrinol Metab Clin North Am，2002，31（4）：885?893，viii.
[11]	Bhutia YD，Kopel JJ，Lawrence JJ，et al. Plasma membrane Na?-coupled citrate transporter （SLC13A5） and neonatal epileptic encephalopathy［J］. Molecules，2017，22（3）：E378.
[12]	Markovich D. Na⁺-sulfate cotransporter SLC13A1［J］. Pflugers Arch，2014，466（1）：131?137.
[13]	Breljak D，Ljubojevi? M，Hagos Y，et al. Distribution of organic anion transporters NaDC3 and OAT1-3 along the human nephron［J］. Am J Physiol Renal Physiol，2016，311（1）：F227?F238.
[14]	Zhang Z，Aung ZT，Simmons DG，et al. Molecular analysis of sequence and splice variants of the human SLC13A4 sulfate transporter［J］. Mol Genet Metab，2017，121（1）：35?42.
[15]	Willmes DM，Kurzbach A，Henke C，et al. The longevity gene INDY （I''''m Not Dead Yet） in metabolic control：potential as pharmacological target［J］. Pharmacol Ther，2018，185：1?11.
[16]	Irizarry AR，Yan GR，Zeng QQ，et al. Defective enamel and bone development in sodium-dependent citrate transporter （NaCT） Slc13a5 deficient mice［J］. PLoS One，2017，12（4）：e0175465.
[17]	Williams NC，O''''Neill LAJ. A role for the Krebs cycle intermediate citrate in metabolic reprogramming in innate immunity and inflammation［J］. Front Immunol，2018，9：141.
[18]	Gregolin C，Ryder E，Kleinschmidt AK，et al. Molecular characteristics of liver acetyl CoA carboxylase［J］. Proc Natl Acad Sci U S A，1966，56（1）：148?155.
[19]	Ros S，Schulze A. Balancing glycolytic flux：the role of 6-phosphofructo-2-kinase/fructose 2，6-bisphosphatases in cancer metabolism［J］. Cancer Metab，2013，1（1）：8.
[20]	Fu JY，Kemp RG. Activation of muscle fructose 1，6-diphosphatase by creatine phosphate and citrate［J］. J Biol Chem，1973，248（3）：1124?1125.
[21]	Poolsri WA，Phokrai P，Suwankulanan S，et al. Combination of mitochondrial and plasma membrane citrate transporter inhibitors inhibits de novo lipogenesis pathway and triggers apoptosis in hepatocellular carcinoma cells［J］. Biomed Res Int，2018，2018：3683026.
[22]	Nielsen TT. Plasma citrate in relation to glucose and free fatty acid metabolism in man［J］. Dan Med Bull，1983，30（6）：357-378.
[23]	Wang PY，Neretti N，Whitaker R，et al. Long-lived Indy and calorie restriction interact to extend life span［J］. Proc Natl Acad Sci U S A，2009，106（23）：9262-9267.
[24]	Martinez-Beamonte R，Navarro MA，Guillen N，et al. Postprandial transcriptome associated with virgin olive oil intake in rat liver［J］. Front Biosci （Elite Ed），2011，3：11-21.
[25]	Etcheverry A，Aubry M，de Tayrac M，et al. DNA methylation in glioblastoma：impact on gene expression and clinical outcome［J］. BMC Genomics，2010，11：701.
[26]	Neusch?fer-Rube F，Lieske S，Kuna M，et al. The mammalian INDY homolog is induced by CREB in a rat model of type 2 diabetes［J］. Diabetes，2014，63（3）：1048?1057.
[27]	Neusch?fer-Rube F，Schraplau A，Schewe B，et al. Arylhydrocarbon receptor-dependent mIndy （Slc13a5） induction as possible contributor to benzo［a］Pyrene-induced lipid accumulation in hepatocytes［J］. Toxicology，2015，337：1?9.
[28]	Li LH，Li HS，Garzel B，et al. SLC13A5 is a novel transcriptional target of the pregnane X receptor and sensitizes drug-induced steatosis in human liver［J］. Mol Pharmacol，2015，87（4）：674?682.
[29]	Brachs S，Winkel AF，Tang H，et al. Inhibition of citrate cotransporter Slc13a5/mINDY by RNAi improves hepatic insulin sensitivity and prevents diet-induced non-alcoholic fatty liver disease in mice［J］. Mol Metab，2016，5（11）：1072?1082.
[30]	Pesta DH，Perry RJ，Guebre-Egziabher F，et al. Prevention of diet-induced hepatic steatosis and hepatic insulin resistance by second generation antisense oligonucleotides targeted to the longevity gene mIndy （Slc13a5）［J］. Aging （Albany NY），2015，7（12）：1086?1093.
[31]	Li ZH，Li DC，Choi EY，et al. Silencing of solute carrier family 13 member 5 disrupts energy homeostasis and inhibits proliferation of human hepatocarcinoma cells［J］. J Biol Chem，2017，292（33）：13890?13901.
[32]	Sun JK，Aluvila S，Kotaria R，et al. Mitochondrial and plasma membrane citrate transporters：discovery of selective inhibitors and application to structure/function analysis［J］. Mol Cell Pharmacol，2010，2（3）：101?110.
[33]	Pajor AM，de Oliveira CA，Song K，et al. Molecular basis for inhibition of the Na⁺/citrate transporter NaCT （SLC13A5） by dicarboxylate inhibitors［J］. Mol Pharmacol，2016，90（6）：755?765.
[34]	Huard K，Gosset JR，Montgomery JI，et al. Optimization of a dicarboxylic series for in vivo inhibition of citrate transport by the solute carrier 13 （SLC13） family［J］. J Med Chem，2016，59（3）：1165?1175.
[35]	Rives ML，Shaw M，Zhu B，et al. State-dependent allosteric inhibition of the human SLC13A5 citrate transporter by hydroxysuccinic acids，PF-06649298 and PF-06761281［J］. Mol Pharmacol，2016，90（6）：766?774.

[1]	QIAN Qianqian, LI Guozhi, TIAN Hong, GAO Xiangdong. Design, preparation, and antitumor activity of fusion protein vaccine based on tumor antigen PBK[J]. Journal of China Pharmaceutical University, 2024, 55(5): 657-665. DOI: 10.11665/j.issn.1000-5048.2024030801
[2]	ZHOU Hongyou, GAO Xiangdong, YAO Wenbing, TIAN Hong. Screening of adjuvant for PD-L1 vaccine based on nitrated T cell epitope[J]. Journal of China Pharmaceutical University, 2024, 55(3): 397-403. DOI: 10.11665/j.issn.1000-5048.2023032801
[3]	LI Mengyuan, JIANG Xiaomeng, SUN Qinyi, GUO Wei. Research progress of CAR-T immunotherapy in solid tumors combined with new strategies[J]. Journal of China Pharmaceutical University, 2023, 54(4): 443-449. DOI: 10.11665/j.issn.1000-5048.2023030101
[4]	SHAO Shishuai, DUAN Shukang, TIAN Hong, YAO Wenbing, GAO Xiangdong. Design and antitumor activity of programmed cell death ligand 1 epitope peptide vaccine[J]. Journal of China Pharmaceutical University, 2023, 54(2): 245-254. DOI: 10.11665/j.issn.1000-5048.2023022803
[5]	WANG Zhenghao, GAO Yafeng, ZHANG Lianjun, LIU Chang. Research progress of T cell anti-tumor function regulated by endoplasmic reticulum stress[J]. Journal of China Pharmaceutical University, 2022, 53(5): 518-524. DOI: 10.11665/j.issn.1000-5048.20220502
[6]	YAO Zheng, LI Zihan, GAO Liming, HU Xing, CHEN Yan, PAN Wenqi, LI Qian. Advances of research on CAR-T cell immunotherapy for solid tumors[J]. Journal of China Pharmaceutical University, 2021, 52(4): 496-504. DOI: 10.11665/j.issn.1000-5048.20210413
[7]	XIA Xuefei, ZHANG Li, LUO Jianhua, YAO Wenbing, GAO Xiangdong, TIAN Hong. Design and antitumor activity of immune checkpoint B7-H3 epitope vaccine[J]. Journal of China Pharmaceutical University, 2021, 52(4): 472-479. DOI: 10.11665/j.issn.1000-5048.20210410
[8]	CHEN Hongmei, KANG Yanliang, LIU Li, YAO Wenbing, TIAN Hong. Effects of different immunogenic amino acids in PD-L1 vaccine on the differentiation of T cell subsets[J]. Journal of China Pharmaceutical University, 2020, 51(3): 349-356. DOI: 10.11665/j.issn.1000-5048.20200313
[9]	JIANG Liangliang, JIANG Tao, LUO Jianhua, YAO Wenbing, TIAN Hong. A novel human immune system mice model for assessing the immunogenicity of cancer vaccines[J]. Journal of China Pharmaceutical University, 2019, 50(6): 734-742. DOI: 10.11665/j.issn.1000-5048.20190615
[10]	SUN Zhan-yi, CAI Hui, HUANG Zhi-hua, SHI Lei, CHEN Yong-xiang, LI Yan-mei. Advances of glycopeptide-associated tumor vaccines[J]. Journal of China Pharmaceutical University, 2012, 43(2): 97-106.

Cited By

Get Citation

PDF

XML

Article views PDF downloads

Turn off MathJax

Article Contents

Abstract

References

Progress of SLC13A5 as a potential pharmacological target of metabolic diseases

Abstract

References

Related Articles

Catalog

Progress of SLC13A5 as a potential pharmacological target of metabolic diseases

Abstract

References

Related Articles

Catalog

Export File

Citation

Format

Content