Medical Research Laboratory, Department of Clinical Medicine, Endocrinology and internal medicine, Aarhus University Hospital, Palle Juul-Jensens Boulevard 165, 8200 Aarhus N, Denmark.
Medical Research Laboratory, Department of Clinical Medicine, Endocrinology and internal medicine, Aarhus University Hospital, Palle Juul-Jensens Boulevard 165, 8200 Aarhus N, Denmark; Steno Diabetes Center Aarhus, Aarhus University Hospital, Hedeager 3, 2., 8200 Aarhus N, Denmark.
Metabolism. 2020 Apr;105:154188. doi: 10.1016/j.metabol.2020.154188. Epub 2020 Feb 18.
Lipoprotein lipase (LPL) catalyzes the hydrolysis of circulating triglycerides into free fatty acids (FFA) and thereby promotes FFA uptake in peripheral tissues. LPL is negatively regulated by angiopoietin-like protein 4 (ANGPTL4) presumably by an FFA-dependent mechanism. Growth hormone (GH) suppresses LPL activity, but it is unknown whether this is mediated by FFA and ANGPTL4. Therefore, we investigated the concerted effect of GH on ANGPTL4 and LPL in the presence and absence of lipolysis in two in vivo studies in human subjects.
In a randomized, placebo-controlled, cross-over study, nine obese men were examined after injection of 1) a GH bolus, and 2) a GH-receptor antagonist followed by four adipose tissue biopsies obtained over a 5-h period. In a second study, nine hypopituitary men were examined in a 2 × 2 factorial design including GH and acipimox (an anti-lipolytic agent), with biopsies from adipose tissue and skeletal muscle obtained during a basal period and a subsequent hyperinsulinemic-euglycemic clamp. The mRNA expression of ANGPTL4 and LPL as well as LPL activity were analyzed in the biopsies.
In both studies, GH increased serum FFA levels, upregulated ANGPTL4 mRNA expression and suppressed LPL activity. In study 2, acipimox completely suppressed FFA levels and antagonized the effects of GH on ANGPTL4 and LPL.
These human in vivo studies demonstrate that GH upregulates ANGPTL4 mRNA and suppresses LPL activity via an FFA-dependent mechanism.
脂蛋白脂肪酶（LPL）催化循环甘油三酯水解为游离脂肪酸（FFA），从而促进外周组织中 FFA 的摄取。ANGPTL4 负调节 LPL，推测是通过 FFA 依赖的机制。生长激素（GH）抑制 LPL 活性，但尚不清楚这是否通过 FFA 和 ANGPTL4 介导。因此，我们在两项人体研究中，在存在和不存在脂肪分解的情况下，研究了 GH 对 ANGPTL4 和 LPL 的协同作用。
在一项随机、安慰剂对照、交叉研究中，在给 9 名肥胖男性注射 1）GH 脉冲和 2）GH 受体拮抗剂后，在 5 小时内采集 4 次脂肪组织活检，观察其变化。在第二项研究中，9 名垂体功能减退男性在 2×2 析因设计中接受 GH 和 acipimox（一种抗脂肪分解剂）检查，在基础期和随后的高胰岛素-正常血糖钳夹期间采集脂肪组织和骨骼肌活检。分析活检中 ANGPTL4 和 LPL 的 mRNA 表达和 LPL 活性。
在两项研究中，GH 均增加血清 FFA 水平，上调 ANGPTL4 mRNA 表达并抑制 LPL 活性。在研究 2 中，acipimox 完全抑制 FFA 水平，并拮抗 GH 对 ANGPTL4 和 LPL 的作用。
这些人体体内研究表明，GH 通过 FFA 依赖的机制上调 ANGPTL4 mRNA 并抑制 LPL 活性。
