Liver fatty acid-binding protein and obesity.
Liver fatty acid-binding protein and obesity.
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DOI：
10.1016/j.jnutbio.2010.01.005
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发表时间：
2010-11
期刊：
影响因子：
--
通讯作者：
Schroeder F
中科院分区：
文献类型：
--
作者：
Atshaves BP;Martin GG;Hostetler HA;McIntosh AL;Kier AB;Schroeder F
虽然低水平的未酯化长链脂肪酸（LCFA）是膳食和内源性脂肪的正常代谢中间体，但LCFA也是关键受体/酶的有效调节剂，并且在高水平下成为细胞内的有毒去污剂。LCFA水平升高与糖尿病、肥胖和代谢综合征有关。因此，哺乳动物进化出脂肪酸结合蛋白（FABP），其结合/隔离胞质溶胶中的这些潜在毒性游离脂肪酸，并将其呈递给氧化（线粒体，过氧化物酶体）或储存（内质网，脂滴）细胞器中快速去除。哺乳动物具有大的（15个成员）FABP家族，其中多个成员出现在单个细胞类型中。首先描述的FABP，肝-FABP（L-FABP，或FABP 1），在肝以及肠和肾中以非常高的水平（2-5%的胞质蛋白）表达。由于L-FABP在体外和培养细胞中促进LCFA的摄取和代谢，因此预期L-FABP的功能异常或丧失将减少肝脏LCFA摄取/氧化，从而增加可用于肌肉中氧化和/或脂肪中储存的LCFA。这一预测证实了在体外与分离的肝切片和培养的原代肝细胞从L-FABP基因消融小鼠。尽管随意喂食对照饮食时摄食量没有改变，但L-FABP缺失小鼠表现出年龄和性别依赖性的体重增加和脂肪组织质量增加。肥胖表型在成对喂食高脂肪饮食的L-FABP缺失小鼠中加剧。与其他研究结果一起，这些数据表明L-FABP可能在预防年龄或饮食诱导的肥胖中发挥重要作用。
While low levels of unesterified long chain fatty acids (LCFAs) are normal metabolic intermediates of dietary and endogenous fat, LCFAs are also potent regulators of key receptors/enzymes, and at high levels become toxic detergents within the cell. Elevated levels of LCFAs are associated with diabetes, obesity, and metabolic syndrome. Consequently, mammals evolved fatty acid binding proteins (FABPs) that bind/sequester these potentially toxic free fatty acids in the cytosol and present them for rapid removal in oxidative (mitochondria, peroxisomes) or storage (endoplasmic reticulum, lipid droplets) organelles. Mammals have a large (15 member) family of FABPs with multiple members occurring within a single cell type. The first described FABP, liver-FABP (L-FABP, or FABP1), is expressed in very high levels (2-5% of cytosolic protein) in liver as well as intestine and kidney. Since L-FABP facilitates uptake and metabolism of LCFAs in vitro and in cultured cells, it was expected that abnormal function or loss of L-FABP would reduce hepatic LCFA uptake/oxidation and thereby increase LCFAs available for oxidation in muscle and/or storage in adipose. This prediction was confirmed in vitro with isolated liver slices and cultured primary hepatocytes from L-FABP gene-ablated mice. Despite unaltered food consumption when fed a control diet ad libitum, the L-FABP null mice exhibited age- and sex-dependent weight gain and increased fat tissue mass. The obese phenotype was exacerbated in L-FABP null mice pair-fed a high fat diet. Taken together with other findings, these data suggest that L-FABP could have an important role in preventing age- or diet-induced obesity.
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影响因子：
1.9
作者：
Atshaves, Barbara P.;McIntosh, Avery L.;Storey, Stephen M.;Landrock, Kerstin K.;Kier, Ann B.;Schroeder, Friedhelm
通讯作者：
Schroeder, Friedhelm
影响因子：
15.9
作者：
BAIER, LJ;SACCHETTINI, JC;PROCHAZKA, M
通讯作者：
PROCHAZKA, M
影响因子：
4.1
作者：
Antonenkov, VD;Sormunen, RI;Hiltunen, JK
通讯作者：
Hiltunen, JK
DOI：
10.1016/0005-2760(95)00114-r
发表时间：
1995-09-14
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA-LIPIDS AND LIPID METABOLISM
影响因子：
--
作者：
BESNARD, P;FOUCAUD, L;CARLIER, H
通讯作者：
CARLIER, H
影响因子：
5.5
作者：
Atshaves, BP;McIntosh, AL;Schroeder, F
通讯作者：
Schroeder, F