Dipartimento di Medicina e Chirurgia Traslazionale, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.
Dipartimento di Sicurezza e Bioetica, Sezione di Farmacologia, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.
IUBMB Life. 2021 Jul;73(7):978-984. doi: 10.1002/iub.2504. Epub 2021 May 28.
Ghrelin and its endogenous antagonist liver-expressed antimicrobial peptide-2 (LEAP-2) are involved in GH secretion and glucose/lipids metabolism. LEAP-2 expression in conditions of metabolic impairment may be upregulated, usually pairing with a concomitant reduction in ghrelin secretion. Adult growth hormone deficiency (aGHD) is characterized by insulin resistance, weight gain, and increased fat mass. Therefore, the primary endpoint of this cross-sectional observational pilot study was to compare circulating LEAP-2 and ghrelin levels in aGHD and healthy controls. Thirty patients were included in the study. Group A included adult GHD: 15 patients, 8 females, and 7 males. Median and interquartile range age of the group was 53 (41-57) years, while BMI was 27.1 (25-35) kg/m . Group B was formed by 15 healthy controls (10 females and 5 males). Median and interquartile range age was 47 (36-57) years, while BMI 22.9 (20.8-33.1) kg/m . They were evaluated for serum glucose and insulin, HOMA-index, QUICKI-index, total/LDL/HDL cholesterol, triglycerides, IGF-1, ghrelin, and LEAP-2. Ghrelin levels in the aGHD group were significantly lower than in healthy controls. In contrast, LEAP-2 showed a trend toward higher levels, although the differences were not significant. However, the LEAP-2/Ghrelin ratio was significantly higher in aGHD. No significant correlations between ghrelin and LEAP-2 with BMI and HOMA index were found in aGHD population. However, a significant inverse correlation (r = 0.15, p = .047) between BMI and ghrelin was evidenced when considering the whole population. Taken together, these results may suggest a body adaptation to a metabolic scenario typical of aGHD. The decrease in ghrelin production could prevent further weight gain and fat mass increase, although losing its secretagogue effect.
生长激素释放肽（ghrelin）及其内源性拮抗剂肝表达抗菌肽-2（LEAP-2）参与 GH 分泌和葡萄糖/脂质代谢。在代谢受损的情况下，LEAP-2 的表达可能上调，通常伴随着生长激素释放肽（ghrelin）分泌的减少。成人生长激素缺乏症（aGHD）的特征是胰岛素抵抗、体重增加和脂肪量增加。因此，这项横断面观察性初步研究的主要终点是比较 aGHD 和健康对照组的循环 LEAP-2 和生长激素释放肽（ghrelin）水平。研究纳入了 30 名患者。A 组包括成年 GHD：15 名患者，8 名女性和 7 名男性。组的中位数和四分位距年龄为 53（41-57）岁，而 BMI 为 27.1（25-35）kg/m 。B 组由 15 名健康对照者（10 名女性和 5 名男性）组成。中位数和四分位距年龄为 47（36-57）岁，而 BMI 为 22.9（20.8-33.1）kg/m 。对他们的血清葡萄糖和胰岛素、HOMA 指数、QUICKI 指数、总胆固醇/LDL/HDL 胆固醇、甘油三酯、IGF-1、生长激素释放肽（ghrelin）和 LEAP-2 进行了评估。aGHD 组的生长激素释放肽（ghrelin）水平明显低于健康对照组。相反，LEAP-2 水平呈上升趋势，但差异无统计学意义。然而，aGHD 中 LEAP-2/生长激素释放肽（ghrelin）的比值显著升高。在 aGHD 人群中，生长激素释放肽（ghrelin）和 LEAP-2 与 BMI 和 HOMA 指数之间无显著相关性。然而，当考虑整个人群时，发现 BMI 与生长激素释放肽（ghrelin）之间存在显著的负相关（r=0.15，p=0.047）。综上所述，这些结果可能表明机体对 aGHD 典型代谢情况的适应。生长激素释放肽（ghrelin）产生的减少可能会阻止体重进一步增加和脂肪量增加，尽管失去了其促分泌作用。
