Steno Diabetes Center Aarhus, Aarhus University Hospital, Aarhus, Denmark.
Medical Research Laboratory, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
Clin Endocrinol (Oxf). 2020 Dec;93(6):672-677. doi: 10.1111/cen.14290. Epub 2020 Aug 3.
Acylated ghrelin increases growth hormone (GH) and adrenocorticotrophic hormone (ACTH) secretion from the anterior pituitary gland. Additionally, it increases free fatty acid levels independently of GH and ACTH, but the impact of ghrelin on fatty acid turnover has not been determined. This study was designed to test whether acylated ghrelin directly increases the turnover rate of fatty acids.
Eight hypopituitary patients on stable replacement with GH and hydrocortisone were included in a randomized, double-blinded, placebo-controlled crossover study including two study days: (a) infusion of acylated ghrelin and (b) infusion of saline. The study day comprised a basal period (t = 0-120 minutes) and a hyperinsulinaemic-euglycemic clamp period (t = 120-300 minutes). Whole-body lipolysis was estimated at t = 90-120 and t = 270-300 minutes with a palmitate isotope dilution technique.
Infusion of acylated ghrelin resulted in 10 times increased total ghrelin area under the curve (AUC) levels in the basal period and 15 times increased AUC levels in the clamp period compared with saline infusion (P < .001). GH levels were largely unaffected by ghrelin compared to saline infusion during both the basal and clamp period, but cortisol levels increased by 15% after ghrelin compared to saline infusion in the basal period (P = .03). Palmitate turnover was increased by 43% in the basal period (difference: 77 (20) µmol/min, P = .01) and unchanged in the clamp period (difference 0.9 (17) µmol/min, P = 1.0) after ghrelin compared to saline infusion.
Our results support the hypothesis that pharmacological levels of acylated ghrelin directly activate lipolysis at the whole-body level.
酰化 ghrelin 可增加垂体前叶生长激素 (GH) 和促肾上腺皮质激素 (ACTH) 的分泌。此外，它可独立于 GH 和 ACTH 增加游离脂肪酸水平，但 ghrelin 对脂肪酸周转的影响尚未确定。本研究旨在测试酰化 ghrelin 是否直接增加脂肪酸的周转率。
纳入 8 名接受 GH 和氢化可的松稳定替代治疗的垂体功能减退症患者，进行随机、双盲、安慰剂对照交叉研究，包括 2 个研究日：(a) 酰化 ghrelin 输注和 (b) 生理盐水输注。研究日包括基础期 (t = 0-120 分钟) 和高胰岛素-正常血糖钳夹期 (t = 120-300 分钟)。在 90-120 分钟和 270-300 分钟时，使用棕榈酸同位素稀释技术估计全身脂肪分解。
与生理盐水输注相比，酰化 ghrelin 输注导致基础期总 ghrelin 曲线下面积 (AUC) 增加 10 倍，钳夹期 AUC 增加 15 倍 (P <.001)。与生理盐水输注相比，ghrelin 对 GH 水平的影响在基础期和钳夹期均不大，但在基础期 ghrelin 输注后皮质醇水平升高 15% (P =.03)。与生理盐水输注相比，ghrelin 输注可使基础期棕榈酸周转率增加 43% (差异：77 (20) µmol/min，P =.01)，而钳夹期无变化 (差异 0.9 (17) µmol/min，P = 1.0)。
我们的结果支持这样的假设，即药理学水平的酰化 ghrelin 可直接激活全身脂肪分解。
