Department of Physiology and Pharmacology, Texas A&M University, TVMC, College Station, TX 77843-4466, USA.
J Nutr Biochem. 2010 Nov;21(11):1015-32. doi: 10.1016/j.jnutbio.2010.01.005.
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 in 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.
尽管低水平的未酯化长链脂肪酸 (LCFAs) 是饮食和内源性脂肪的正常代谢中间产物，但 LCFAs 也是关键受体/酶的有效调节剂，并且在高水平下，它们在细胞内成为有毒的清洁剂。LCFAs 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)，这些蛋白可以在细胞质中结合/隔离这些潜在的有毒游离脂肪酸，并将其迅速递送至氧化（线粒体、过氧化物酶体）或储存（内质网、脂滴）细胞器中。哺乳动物有一个庞大的（15 个成员）FABP 家族，其中多个成员存在于单个细胞类型中。第一个描述的 FABP，肝 FABP（L-FABP 或 FABP1），在肝脏以及肠道和肾脏中以非常高的水平（细胞质蛋白的 2-5%）表达。由于 L-FABP 促进了体外和培养细胞中 LCFAs 的摄取和代谢，因此人们预计 L-FABP 的异常功能或缺失会减少肝脏 LCFAs 的摄取/氧化，从而增加肌肉中可用于氧化的 LCFAs 和/或脂肪组织中的储存。这一预测在体外使用从 L-FABP 基因敲除小鼠分离的肝切片和培养的原代肝细胞得到了证实。尽管在自由进食对照饮食时，未改变的食物消耗，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。在 L-FABP 缺失小鼠进行高脂饮食喂养时，肥胖表型更加严重。结合其他发现，这些数据表明 L-FABP 可能在预防年龄或饮食引起的肥胖中发挥重要作用。
