溶质载体SLC家族在非酒精性脂肪性肝病中的研究进展

doi:10.16288/j.yczz.22-238

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Hereditas(Beijing) ›› 2022, Vol. 44 ›› Issue (10): 881-898.doi: 10.16288/j.yczz.22-238

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Progress of solute carrier SLC family in nonalcoholic fatty liver disease

Zhiquan Tang(), Li Shi, Jing Xiong()

School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China

Received:2022-07-16 Revised:2022-09-22 Online:2022-10-20 Published:2022-09-30
Contact: Xiong Jing E-mail:1350312679@qq.com;jxiong@cpu.edu.cn
Supported by:
the National Natural Science Foundation of China(82070883);the National Natural Science Foundation of China(82273982);the National Natural Science Foundation of Jiangsu Province(BK20221525);and the Scientific Research Foundation for High-level Faculty, China Pharmaceutical University

Abstract

Abstract:

Nonalcoholic fatty liver disease is closely related to obesity and type 2 diabetes mellitus, and is one of the components of metabolic syndrome. Due to the complexity of its pathogenesis, there is no effective drug treatment to date. Solute carrier transporters are associated with a variety of metabolic diseases and are abundantly expressed in the liver. They participate in the transport of a variety of nutrients and metabolites, regulate nutrient supply, metabolic transformation, energy balance and oxidative stress, and modulate the physiological functions of liver. Particularly, it is important that some of these SLC transporters have become new targets for drug development. In this review, we summarize the role of SLC in the transport of nutrients and liver metabolites and its correlation with NAFLD, and reveal the potential of SLC as a target for the development of new drugs for NAFLD treatment so as to provide a new choice for the treatment of the disease.

Key words: nonalcoholic fatty liver disease, solute carrier SLC family, glucose and lipid metabolism

Zhiquan Tang, Li Shi, Jing Xiong. Progress of solute carrier SLC family in nonalcoholic fatty liver disease[J]. Hereditas(Beijing), 2022, 44(10): 881-898.

Figures/Tables 3

Table 1

The cellular localization, physiological functions and expression of the SLC family members related to NAFLD"

基因名称	别称	定位	生理功能	表达情况	参考文献
Slc2a1	Glut1	细胞膜	转运细胞膜外葡萄糖进入细胞内	↓	[14,[15]
Slc2a2	Glut2	细胞膜	转运细胞膜外葡萄糖进入细胞内	↓	[16,[17]
Slc2a4	Glut4	细胞膜	转运细胞膜外葡萄糖进入细胞内	↓	[18]
Slc2a5	Glut5	细胞膜	转运细胞膜外果糖进入细胞内	↓	[28,[29]
Slc2a8	Glut8	细胞膜	转运细胞膜外葡萄糖和果糖进入细胞内	↓	[30~33]
Slc2a9	Glut9/Uratv1	细胞膜	转运细胞膜外尿酸、葡萄糖和果糖进入细胞内	↓	[20,[21]
Slc5a2	Sglt2	细胞膜	转运细胞膜外葡萄糖进入细胞内	↑	[22,23,24, 25]
Slc5a10	Sglt5	细胞膜	转运细胞膜外果糖进入细胞内	↓	[34]
Slc13a1	Nas1	细胞膜	转运细胞膜外硫酸盐进入细胞内	↓	[35,[48]
Slc13a2	Nadc1	细胞膜	转运细胞膜外柠檬酸盐进入细胞内	↓	[37,39,40]
Slc13a3	Nadc3	细胞膜	转运细胞膜外α-酮戊二酸盐进入细胞内	↓	[41,43,44]
Slc13a5	Nact	细胞膜	转运细胞膜外琥珀酸进入细胞内	↓	[45~47]
Slc16a1	Mct1	细胞膜	促进细胞内单羧酸盐外排	↑	[50~52]
Slc16a4	Mct4	细胞膜	转运细胞膜外单羧酸盐进入细胞内	↑	[53,[54]
Slc16a10	Mct10	细胞膜	促进细胞内芳香族氨基酸外排	↓	[55~57]
Slc16a11	Mct11	内质网细胞膜	转运单羧酸盐进出细胞	↑	[59,61,62]
Slc16a13	Mct13	细胞膜	转运乳酸进入细胞内	↑	[63,[64]
Slc22a5	Octn2	细胞膜	转运肉碱进入细胞内	↓	[68,69,70,71]
Slc22a7	Oat2	细胞膜	转运cGMP、烟酸和烟酰胺进入细胞内	↓	[72,~74]
Slc22a9	Oat4	细胞膜	转运丁酸进入细胞内	↓	[75,[77]
Slc22a12	Oat4l/Urat1	细胞膜	转运尿酸盐进入细胞内	↑	[79]
Slc25a1	Ctp	线粒体	促进柠檬酸盐从线粒体转运到细胞浆	↑	[93]
Slc25a7	Ucp1	线粒体	促进长链脂肪酸从线粒体内膜到外膜的转移及质子从线粒体外膜到内膜的转移	↓	[85,86,87,88]
Slc25a8	Ucp2	线粒体	同Ucp1	↓	[89~,91,]
Slc25a9	Ucp3	线粒体	同Ucp1	↓	[92]
Slc25a10	Dic	线粒体	促进柠檬酸盐、琥珀酸盐从线粒体转运到细胞浆	↑	[94,95,96,97]
Slc25a11	Ogc	线粒体	促进α-酮戊二酸盐从线粒体转运到细胞浆及谷胱甘肽从细胞浆转运到线粒体	↓	[98,[99]
Slc25a13	Agc2	线粒体	促进天冬氨酸从线粒体转运到细胞浆及谷胱甘肽从细胞浆转运到线粒体	↓	[101,102,103,104]
Slc25a20	Cac	线粒体	促进游离肉碱从线粒体转运到细胞浆及酰基肉碱从细胞浆转运到线粒体	↓	[105]
Slc25a24	Apc1	线粒体	促进线粒体内膜上磷酸盐和核苷酸的转运	↑	[106~108,]
Slc27a2	Fatp2	细胞膜	转运长链脂肪酸进入细胞内	↑	[111,[112]
Slc27a5	Fatp5	细胞膜	转运长链脂肪酸进入细胞内	↑	[113,[114]
Slc30a8	Znt8	细胞膜	促进胰岛素分泌颗粒膜上锌离子外排	↓	[115~117,]

Table 1

Table 2

Fig. 1

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靶点	药物	作用	表型	机制	参考文献
SLC2A2	丁酸盐 GW501516 瑞舒伐他汀	↑	减轻肝脏炎症和脂肪变性	抑制Toll样受体和NF-κB激活	[118]
			减少肝细胞肿胀和炎细胞浸润	激活PPARδ	[119]
			减轻肝脏脂肪变性	抑制HMG-CoA还原酶	[120]
SLC2A4	乳酸	↑	改善胰岛素抵抗	激活GPR81	[121]
	淫羊藿苷		减少脂质积累和细胞凋亡	激活AMPKα1-PGC-1α	[122]
	二甲双胍		降低肝脏氧化应激和体重		[123]
	硝酸芬替康唑		抑制肝脏炎症反应		[124]
SLC2A5	洋甘菊提取物	↑	减轻肝脏脂肪变性	抑制CHREBP	[125]
SLC5A2	恩格列净	↓	降低血糖和肝脏脂肪含量	抑制葡萄糖重吸收	[126]
SLC13A5	PF-06649298	↑	降低血糖和肝脏脂肪含量	抑制转运体活性	[127]
SLC13A5	姜黄素	↑	减少肝脏脂肪累积和氧化应激	抑制促炎巨噬细胞活化	[128]
SLC22A5	L-肉碱	↑	降低肝脏脂肪含量和炎症损伤	促进脂肪酸氧化	[129]
SLC22A7	PF-06835919	↑	降低肝脏脂肪含量和体重	抑制己糖激酶	[130]
SLC25A7	Linifanib	↑	减轻肝脏氧化应激和炎症	抑制STAT3	[131]
SLC54A1	MSDC-0602K	↑	减轻肝脏炎症	增加胰岛素敏感性	[132]

Progress of solute carrier SLC family in nonalcoholic fatty liver disease

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