Vamvini Maria T, Hamnvik Ole-Petter, Sahin-Efe Ayse, Gavrieli Anna, Dincer Fadime, Farr Olivia M, Mantzoros Christos S
Division of Endocrinology (M.T.V., O.-P.H., A.S.-E., A.G., F.D., O.M.F., C.S.M.), Beth-Israel Deaconess Medical Center/Harvard Medical School, Boston, Massachusetts 02215; Department of Internal Medicine (M.T.V.), Mt Auburn Hospital, Harvard Medical School, Cambridge, Massachusetts 02138; and Division of Endocrinology, Diabetes, and Hypertension (O.-P.H.), Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02054.
J Clin Endocrinol Metab. 2016 May;101(5):1989-97. doi: 10.1210/jc.2015-4141. Epub 2016 Mar 10.
The spectrum of lipid-induced changes in the secretion of hormones important in energy homeostasis has not yet been fully elucidated.
To identify potential incretin-like effects in response to lipid administration, we examined the short-term effect of iv vs oral lipids on key molecules regulating energy homeostasis. Design, Intervention, and Participants: After a 10-hour overnight fast, 26 subjects were randomized to receive an oral lipid load, a 10% iv lipid emulsion, a 20% iv lipid emulsion, or an iv saline infusion. We obtained blood samples at 30-minute intervals for the first 2 hours and hourly thereafter for a total of 6 hours.
Circulating levels of insulin, glucose, c-peptide, free fatty acids, incretins (glucagon-like peptide-1, gastric inhibitory polypeptide), glucagon, peptide YY, ghrelin, fibroblast growth factor 21, fetuin A, irisin, omentin, and adiponectin were measured.
Oral lipid ingestion resulted in higher glucagon-like peptide-1, gastric inhibitory polypeptide, glucagon, and peptide YY levels, compared with the other three groups (incremental area under the curve P = .003, P < .001, P < .001, P < .001, respectively). The 20% lipid emulsion, leading to higher free fatty acid levels, resulted in greater insulin, c-peptide, and fibroblast growth factor 21 responses compared with placebo and the other two groups (incremental area under the curve P = .002, P = .005, P < .001, P < .001, respectively). Omentin, adiponectin, fetuin A, and irisin levels were not affected by either mode of lipid administration.
Metabolic responses to lipids depend on the route of administration. Only iv lipids trigger a dose-dependent fibroblast growth factor 21 secretion, which is nonglucagon mediated. Intravenous lipids also induce hyperinsulinemia without concurrent decreases in glucose, a phenomenon observed in insulin-resistant states. Orally administered lipids mostly affect gastrointestinal tract-secreted molecules important in glucose and energy homeostasis such as glucagon, incretins, and peptide YY.
脂质诱导的对能量稳态至关重要的激素分泌变化谱尚未完全阐明。
为了确定脂质给药后的潜在肠促胰岛素样效应，我们研究了静脉注射与口服脂质对调节能量稳态的关键分子的短期影响。设计、干预措施及参与者：经过10小时的夜间禁食后，26名受试者被随机分配接受口服脂质负荷、10%静脉脂质乳剂、20%静脉脂质乳剂或静脉输注生理盐水。在最初2小时内每隔30分钟采集一次血样，此后每小时采集一次，共采集6小时。
测量胰岛素、葡萄糖、C肽、游离脂肪酸、肠促胰岛素（胰高血糖素样肽-1、胃抑制多肽）、胰高血糖素、肽YY、胃饥饿素、成纤维细胞生长因子21、胎球蛋白A、鸢尾素、网膜素和脂联素的循环水平。
与其他三组相比，口服脂质导致胰高血糖素样肽-1、胃抑制多肽、胰高血糖素和肽YY水平升高（曲线下增量面积分别为P = 0.003、P < 0.001、P < 0.001、P < 0.001）。导致游离脂肪酸水平升高的20%脂质乳剂与安慰剂及其他两组相比，引起更大的胰岛素、C肽和成纤维细胞生长因子21反应（曲线下增量面积分别为P = 0.002、P = 0.005、P < 0.001、P < 0.001）。网膜素、脂联素、胎球蛋白A和鸢尾素水平不受脂质给药方式的影响。
对脂质的代谢反应取决于给药途径。只有静脉注射脂质会引发剂量依赖性的成纤维细胞生长因子21分泌，这一过程是非胰高血糖素介导的。静脉注射脂质还会诱导高胰岛素血症，而血糖水平不会同时降低，这是在胰岛素抵抗状态下观察到的一种现象。口服脂质主要影响胃肠道分泌的对葡萄糖和能量稳态重要的分子，如胰高血糖素、肠促胰岛素和肽YY。
