Martin Gregory G, Atshaves Barbara P, McIntosh Avery L, Mackie John T, Kier Ann B, Schroeder Friedhelm
Department of Physiology and Pharmacology and 5Department of Pathobiology, Texas A&M University, Texas Veterinary Medical College, College Station, TX 77843-4467, USA.
J Nutr. 2008 Oct;138(10):1859-65. doi: 10.1093/jn/138.10.1859.
Previous work conducted in our laboratory suggested a role for liver fatty acid-binding protein (L-FABP) in obesity that develops in aging female L-FABP gene-ablated (-/-) mice. To examine this possibility in more detail, cohorts of wild-type (+/+) and L-FABP (-/-) female mice were fed a standard, low-fat, nonpurified rodent diet for up to 18 mo. Various obesity-related parameters were examined, including body weight and fat and lean tissue mass. Obesity in (-/-) mice was associated with increased expression of nuclear receptors that induce PPARalpha (e.g. hepatocyte nuclear factor 1alpha, genotype effect) and of PPARalpha-regulated proteins involved in uptake of free (lipoprotein lipase and fatty acid transport protein, genotype, and/or age effect) and esterified (scavenger receptor class B type 1, genotype effect) long-chain fatty acids (LCFA). Hepatic total lipid and neutral lipid levels were not affected by age or genotype, consistent with absence of gross and histologic steatosis. There was increased mRNA expression of liver proteins involved in LCFA oxidation [mitochondrial 3-oxoacyl-CoA thiolase (genotype effect) and butyryl-CoA dehydrogenase (genotype and/or age effect)], increased expression of LCFA esterification enzymes [glycerol-3-phosphate acyltransferase (age x genotype effect) and acyl-CoA:cholesterol acyltransferase-2 (genotype and/or age effect)], and increased expression of proteins involved in intracellular transfer and secretion of esterified LCFA [liver microsomal triacylglycerol transfer protein (genotype effect), serum apolipoprotein (apo) B (genotype or age effect), and liver apoB (age and age x genotype effect)]. The data support a working model in which obesity development in these mice results from shifts toward reduced energy expenditure and/or more efficient energy uptake in the gut.
我们实验室之前开展的研究表明，肝脏脂肪酸结合蛋白（L-FABP）在衰老的雌性L-FABP基因敲除（-/-）小鼠所发生的肥胖中发挥作用。为了更详细地研究这种可能性，将野生型（+/+）和L-FABP（-/-）雌性小鼠分为几组，给它们喂食标准的低脂非纯化啮齿动物饮食，长达18个月。检测了各种与肥胖相关的参数，包括体重以及脂肪和瘦组织质量。（-/-）小鼠的肥胖与诱导PPARα的核受体（如肝细胞核因子1α，基因型效应）以及参与游离长链脂肪酸（LCFA）摄取（脂蛋白脂肪酶和脂肪酸转运蛋白，基因型和/或年龄效应）和酯化LCFA摄取（B类清道夫受体1型，基因型效应）的PPARα调节蛋白的表达增加有关。肝脏总脂质和中性脂质水平不受年龄或基因型的影响，这与无明显和组织学上的脂肪变性一致。参与LCFA氧化的肝脏蛋白[线粒体3-氧代酰基辅酶A硫解酶（基因型效应）和丁酰辅酶A脱氢酶（基因型和/或年龄效应）]的mRNA表达增加，LCFA酯化酶[甘油-3-磷酸酰基转移酶（年龄×基因型效应）和酰基辅酶A：胆固醇酰基转移酶-2（基因型和/或年龄效应）]的表达增加，以及参与酯化LCFA细胞内转运和分泌的蛋白[肝脏微粒体三酰甘油转移蛋白（基因型效应）、血清载脂蛋白（apo）B（基因型或年龄效应）和肝脏apoB（年龄和年龄×基因型效应）]的表达增加。这些数据支持了一个工作模型，即这些小鼠的肥胖发展是由于能量消耗减少和/或肠道能量摄取效率提高所致。
