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: 2573717
• 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/2573717
• 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 [l-13C]-palmitic acid as a tracer of fatty acid metabolism in healthy subjects homozygous for either the Thr54 form or the Ala54 form of IFABP. 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. We are currently completing the measurements to determine the plasma lipid responses to the mixed meal.

肠脂肪酸结合蛋白（IFABP）存在于人类 以两种形式，其不同之处在于丙氨酸被苏氨酸取代， 氨基酸54。 在体外，苏氨酸形式（Thr 54）被表征为 对长链脂肪酸的结合亲和力比 丙氨酸形式（Ala 54）。 Thr 54形式也与 高血浆胰岛素浓度和胰岛素抵抗 皮马印第安人。 本项目研究是否在体外结合 差异在生理上是显著的。 净膳食脂肪酸 吸收，动力学的外观膳食脂肪酸进入 血浆中，和脂质氧化的时间过程被确定 在掺入[1 - 13 C]-棕榈酸作为 在健康受试者中的脂肪酸代谢的示踪剂， IFABP的Thr 54形式或Ala 54形式。 共有22 受试者（11例Thr 54和11例Ala 54纯合子，14例男性和8例女性） 到目前为止，已经研究过了。 两组在年龄，体重， 和%体脂肪。 休息和24小时能量消耗以及24小时RQ 两组之间也没有差异。 标签总量 24小时内出现在呼吸中的剂量占给药剂量的百分比 没有显著差异（28+/-2% v30 +/-2%），但有一个 在进餐的最后9小时内，标签氧化的趋势较少 Thr 54纯合子比Ala 54纯合子的检测结果（4.7+/-0.5%v 6.1 ± 0.4%，P < 0.06）。 标签的总吸收率不是 组间差异显著。 我们目前正在 完成测量以确定血浆脂质对 混合餐。