Major facilitator superfamily domain-containing protein 2a (MFSD2A) has roles in body growth, motor function, and lipid metabolism.
Major facilitator superfamily domain-containing protein 2a (MFSD2A) has roles in body growth, motor function, and lipid metabolism.
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DOI：
10.1371/journal.pone.0050629
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Silver DL
中科院分区：
文献类型：
--
作者：
Berger JH;Charron MJ;Silver DL
肝脏对禁食的代谢适应主要由核激素受体过氧化物酶体增殖物激活受体α（PPARα）控制，其中PPARα上调编码脂肪酸β氧化和酮生成生化途径的基因。作为鉴定和表征在适应禁食中发挥生理作用的营养调控基因的努力的一部分，我们鉴定了主要易化超家族含结构域蛋白2a（Mfsd 2a）作为肝脏中受PPARα和胰高血糖素信号转导调控的禁食诱导基因。MFSD 2A是与细菌钠-蜜二糖转运蛋白同源的细胞表面蛋白。MFSD 2A的肝脏表达和周转受禁食/再喂养的急性调节，但在脑中的表达是组成性的。相对于野生型小鼠，基因靶向Mfsd 2a敲除小鼠更小、更瘦，并且具有降低的血清、肝脏和棕色脂肪甘油三酯。Mfsd 2a敲除小鼠具有正常的肝脏脂质代谢，但全身能量消耗增加，这可能是由于棕色脂肪组织中的β-氧化增加和自主运动显著增加，但令人惊讶地表现出共济失调的形式。总之，这些结果表明MFSD 2A是一种营养调节基因，在身体生长和发育、运动功能和脂质代谢中起着多种作用。此外，这些数据表明，由MFSD 2A转运的配体在这些生理过程中起重要作用，并等待未来的鉴定。
The metabolic adaptations to fasting in the liver are largely controlled by the nuclear hormone receptor peroxisome proliferator-activated receptor alpha (PPARα), where PPARα upregulates genes encoding the biochemical pathway for β-oxidation of fatty acids and ketogenesis. As part of an effort to identify and characterize nutritionally regulated genes that play physiological roles in the adaptation to fasting, we identified Major facilitator superfamily domain-containing protein 2a (Mfsd2a) as a fasting-induced gene regulated by both PPARα and glucagon signaling in the liver. MFSD2A is a cell-surface protein homologous to bacterial sodium-melibiose transporters. Hepatic expression and turnover of MFSD2A is acutely regulated by fasting/refeeding, but expression in the brain is constitutive. Relative to wildtype mice, gene-targeted Mfsd2a knockout mice are smaller, leaner, and have decreased serum, liver and brown adipose triglycerides. Mfsd2a knockout mice have normal liver lipid metabolism but increased whole body energy expenditure, likely due to increased β-oxidation in brown adipose tissue and significantly increased voluntary movement, but surprisingly exhibited a form of ataxia. Together, these results indicate that MFSD2A is a nutritionally regulated gene that plays myriad roles in body growth and development, motor function, and lipid metabolism. Moreover, these data suggest that the ligand(s) that are transported by MFSD2A play important roles in these physiological processes and await future identification.
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影响因子：
120.7
作者：
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通讯作者：
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10.1073/pnas.1112304108
发表时间：
2011-11-15
影响因子：
11.1
作者：
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通讯作者：
Heidmann, Thierry
DOI：
10.1073/pnas.0902925106
发表时间：
2009-07-21
影响因子：
11.1
作者：
Dupressoir, Anne;Vernochet, Cecile;Heidmann, Thierry
通讯作者：
Heidmann, Thierry