Liver fatty acid binding protein gene ablation enhances age-dependent weight gain in male mice.
Liver fatty acid binding protein gene ablation enhances age-dependent weight gain in male mice.
复制标题
DOI：
10.1007/s11010-008-9989-9
复制
发表时间：
2009-04
影响因子：
4.3
通讯作者：
Schroeder, Friedhelm
中科院分区：
文献类型：
--
作者：
Martin, Gregory G.;Atshaves, Barbara P.;McIntosh, Avery L.;Payne, H. Ross;Mackie, John T.;Kier, Ann B.;Schroeder, Friedhelm
虽然在体外进行的研究和转染的细胞在培养中的肝脂肪酸结合蛋白（L-FABP）在调节脂肪酸氧化和脂肪沉积的作用，这种可能性的生理意义是不完全清楚。为了开始解决这个问题，随着年龄的增长，直到18个月，检查L-FABP基因去除对标准啮齿类动物饲料喂养的雄性小鼠的表型的影响。虽然年轻的（2-3个月）L-FABP缺失小鼠没有显示出视觉上明显的表型，但随着年龄的增加> 9个月，L-FABP缺失小鼠明显更大，由于脂肪和瘦组织质量增加而表现出体重增加。肝脏脂质浓度不受L-FABP基因消融的影响，但三酰甘油除外，其在3月龄小鼠的肝脏中降低了74%。同样，L-FABP基因敲除小鼠的血清脂质水平没有改变，但三酰甘油除外，其在18月龄小鼠的血清中增加。在18月龄L-FABP缺失小鼠中，体重、脂肪组织质量和瘦组织质量的增加伴随着低密度脂蛋白（LDL）受体、过氧化物酶体增殖物激活受体（PPAR）α和PPARα调节蛋白（如脂肪酸转运蛋白（FATP）、脂肪酸移位酶（FAT/CD 36）、肉毒碱棕榈酰转移酶I（CPT I）和脂蛋白脂肪酶（LPL））的肝脏水平增加。胆固醇生物合成的关键酶3-羟基-3-甲基戊二酰辅酶A（HMG-CoA）还原酶在L-FABP敲除小鼠中表达下调。这些发现与L-FABP作为PPARα重要生理调节剂的作用一致。
Although studies performed in vitro and with transfected cells in culture suggest a role for liver fatty acid binding protein (L-FABP) in regulating fatty acid oxidation and fat deposition, the physiological significance of this possibility is not completely clear. To begin to address this question, the effect of L-FABP gene ablation on phenotype of standard rodent chow-fed male mice was examined with increasing age up to 18 mo. While young (2-3 mo) L-FABP null mice displayed no visually obvious phenotype, with increasing age > 9 mo the L-FABP null mice were visibly larger, exhibiting increased body weight due to increased fat and lean tissue mass. Liver lipid concentrations were unaffected by L-FABP gene ablation with the exception of triacylglycerol, which was decreased by 74% in the livers of 3 mo old mice. Likewise, serum lipid levels were not altered in L-FABP null mice with the exception of triacylglycerol, which was increased in the serum of 18 mo old mice. Increased body weight, fat tissue mass, and lean tissue mass in 18 mo old L-FABP null mice were accompanied by increased hepatic levels of low density lipoprotein (LDL) receptor, peroxisome proliferator-activated receptor (PPAR) α, and PPARα-regulated proteins such as fatty acid transport protein (FATP), fatty acid translocase (FAT/CD36), carnitine palmitoyl transferase I (CPT I), and lipoprotein lipase (LPL). A key enzyme in cholesterol biosynthesis, 3-hydroxy-3-methylglutaryl Coenzyme A (HMG-CoA) reductase was down-regulated in L-FABP null mice. These findings were consistent with a proposed role for L-FABP as an important physiological regulator of PPARα.
登录
查看更多内容
影响因子：
4.8
作者：
Binas, B;Danneberg, H;Clark, AJ
通讯作者：
Clark, AJ
DOI：
10.1152/ajpendo.00468.2002
发表时间：
2003-07-01
影响因子：
5.1
作者：
Banks, WA;Farrell, CL
通讯作者：
Farrell, CL
影响因子：
4.8
作者：
Erol, Erdal;Kumar, Leena S.;Binas, Bert
通讯作者：
Binas, Bert
影响因子：
5.5
作者：
Atshaves, BP;McIntosh, AL;Schroeder, F
通讯作者：
Schroeder, F
影响因子：
4.8
作者：
Atshaves, BP;McIntosh, AM;Schroeder, F
通讯作者：
Schroeder, F