FATTY ACID ABSORPTION AND METABOLISM IN PIMA INDIANS

皮马印第安人的脂肪酸吸收和代谢

• 批准号: 6105965
• 负责人: R PRATLEY
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6105965
• 关键词: Native Americans; alanine; blood lipid; clinical research; dietary lipid; fatty acid binding protein; fatty acid metabolism; fatty acids; gastrointestinal nutrient absorption; human subject; long chain fatty acid; nutrition related tag; oxidation; palmitates; radiotracer; threonine

The intestinal fatty acid binding protein (IFABP) is present in humans in two forms which differ by a alanine to threonine substitution at amino acid 54. In vitro, the threonine form (Thr54) is characterized by a two-fold higher binding affinity for long chain fatty acids than the alamino form (Ala54). The Thr54 form also is associated with higher plasma insulin concentrations and insulin resistance in the Pima Indians. This project examines whether the in vitro binding differences are physiologically significant. Triglyceride and fatty acid responses and of lipid oxidation were determined following a standard test meal in healthy subjects homozygous for either the Thr54 form or the Ala54 form of IAFBP. A total of 18 subjects (9 Thr54 and 9 Ala54 homozygotes, 10 males and 8 females) have been studied, thus far. The groups were similar in age, weight, and % body fat. In response to a mixed meal, plasma NEFA concentrations tended to be higher in individuals homozygous for the Thr54 allele than in sex-matched, comparably obese Ala54 controls. On average, NEFA concentrations were ~15% higher in Thr54 homozygotes than in controls, comparable to the previously reported difference. This difference approached statistical significance (P = 0.07) and would likely have been significant had the sample size been larger. The largest differences between groups occurred later in the course of the study, after subjects had been fasting for several hours, rather than immediately after the meal. NEFA concentrations peaked earlier (~7 h) and ~20% higher in Thr54 homozygotes following the high fat feeding. The polymorphism in IFABP did not appear to affect either skeletal muscle or adipose tissue membrane phospholipid fatty acid composition. Plasma insulin concentrations were higher in subjects homozygous for the Thr54 allele. The difference was most marked following a high fat feeding. The higher insulin responses may be due, in part, to the insulin resistance we have previously documented in individuals with the Thr54 allele. Thus, as might be expected from the tissue distribution of the protein, the Thr54 polymorphism in the IFABP appears to affect primarily post-prandial responses to dietary fat. This effect is subtle, however. This protocol has been terminated.

肠脂肪酸结合蛋白（IFABP）是 存在于人类中的两种形式，其区别在于丙氨酸和 氨基酸54处的苏氨酸取代。在体外，苏氨酸形式 （Thr54）的特征在于对TdR的结合亲和力高两倍。 长链脂肪酸比丙氨酸形式（Ala 54）。THR54 形式也与较高的血浆胰岛素浓度有关 和胰岛素抵抗。本项目研究 体外结合差异是否是生理上的 显著甘油三酯和脂肪酸反应以及脂质 在健康人的标准测试餐后测定氧化 Thr54型或Ala54型纯合子受试者 关于IAFBP共18例受试者（9例Thr54和9例Ala54 纯合子，10名男性和8名女性）进行了研究。 各组在年龄、体重和体脂%方面相似。在 对混合餐的反应，血浆NEFA浓度倾向于 Thr54等位基因纯合子个体中， 性别匹配的肥胖Ala54对照。平均而言，NEFA Thr54纯合子中的浓度比Thr54纯合子中的浓度高约15%。 对照组，与先前报告的差异相当。这 差异接近统计学显著性（P = 0.07）， 如果样本量更大的话，可能会很显著。的 组间最大的差异发生在 在研究对象禁食几个小时后， 而不是饭后立即吃。NEFA浓度达到峰值 Thr54纯合子在接种后更早（约7 h），约高20%。 高脂肪喂养。IFABP的多态性似乎并不影响 影响骨骼肌或脂肪组织膜 磷脂脂肪酸组成。血浆胰岛素浓度 在Thr54等位基因纯合子的受试者中更高。的 在高脂肪喂养后差异最显著。的 较高的胰岛素应答可能部分是由于 我们以前记录的个体中的耐药性 Thr54等位基因。因此，正如从组织分布可以预期的那样， 在IFABP中，Thr54多态性似乎 主要影响餐后对膳食脂肪的反应。这种效果是 但是很微妙。此协议已终止。