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: 6162073
• 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/6162073
• 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 alanine 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. Net dietary fatty acid absorption, the kinetics of appearance of dietary fatty acids into plasma, and the time course of lipid oxidation are determined following a standard test meal incorporating [1-13C] -palmitic acid as a tracer of fatty acid metabolism in healthy subjects homozygous for either the Thr54 form or the Ala54 form of IAFBP. A total of 22 subjects (11 Thr54 and 11 Ala54 homozygotes, 14 males and 8 females) have been studied, thus far. The groups were similar in age, weight, and % body fat. Resting and 24-hour energy expenditure and 24-hour RQ also did not differ between the groups. The total amount of label appearing in breath over 24-hours as a percentage of administered dose was not significantly different (28+/- 2% v 30+/-2%), but there was a tendency for less label to be oxidized in the last 9 hours of the meal test in the Thr54 homozygotes than the Ala54 homozygotes (4.7+/-0.5% v 6.1+/-0.4%, p <0.06). Total absorption of the label was not significantly different between the groups. Analysis of triglyceride in insulin responses of the mixed meal suggest sluggish changes in appearance of triglyceride in plasma and Thr54 homozygotes and more pronounced insulin responses, consistent with insulin resistance.

肠道脂肪酸结合蛋白(IFABP)存在于人类体内 在两种形式中，丙氨酸与苏氨酸在 氨基酸54。在体外，苏氨酸形式(Thr54)被表征 对长链脂肪酸的结合亲和力比 丙氨酸形式(丙氨酸54)。Thr54形态也与更高的 猪血浆胰岛素浓度与胰岛素抵抗 印第安人。这个项目检查了体外结合的差异 具有重要的生理意义。膳食脂肪酸净吸收率 膳食脂肪酸进入血浆的动力学及时间 在标准试餐后测定脂质氧化过程 掺入[1-13C]-棕榈酸作为脂肪酸示踪剂 Thr54或Thr54纯合子健康受试者的代谢 IAFBP的Ala54形式。共有22名受试者(11名至54名和11名Ala54名 到目前为止，已经研究了14个男性和8个女性的纯合子。这个 两组在年龄、体重和体脂百分比方面相似。休息和24小时 能量消耗和24小时RQ也没有区别 组。24小时内出现在呼气中的标签总量为 注射剂量的百分比没有显著差异(28+/- 2%v 30+/-2%)，但有被氧化的标记较少的趋势 在最后9个小时的膳食测试中，Thr54纯合子的 Ala54纯合子(4.7+/-0.5%v6.1+/-0.4%，p&lt；0.06)。总吸收 标签的百分比在组之间没有显著差异。 对混合餐中胰岛素反应的甘油三酯分析表明 血浆和Thr54中甘油三酯的出现迟缓变化 纯合子和更明显的胰岛素反应，符合 胰岛素抵抗。