Dept. of Medical, Surgical and Health Sciences - University of Trieste, Italy and Azienda Sanitaria Universitaria Giuliano Isontina (ASUGI), Trieste, Italy.
Dept. of Medical, Surgical and Health Sciences - University of Trieste, Italy and Azienda Sanitaria Universitaria Giuliano Isontina (ASUGI), Trieste, Italy.
Clin Nutr. 2021 Feb;40(2):638-644. doi: 10.1016/j.clnu.2020.06.014. Epub 2020 Jun 25.
BACKGROUND & AIMS: Unacylated ghrelin (UnAG) modulates insulin sensitivity. Low plasma UnAG occurs in obesity and potentially contributes to obesity-associated insulin resistance. We hypothesized that improvements in insulin sensitivity in obese people induced by moderate caloric restriction (CR) may be paralleled and at least in part explained by concurrent increases in UnAG levels.
20 general community obese people were randomly assigned to 16-week CR (n = 11) or control diet (n = 9). We investigated the impact of CR on the interaction between insulin sensitivity changes [area under the curve (AUCg) of glucose infusion to maintain euglycemia during hyperinsulinemic-euglycemic clamp] and plasma total (TotalG), acylated (AG) and Unacylated ghrelin (UnAG). Plasma pro-inflammatory tumor necrosis factor alpha (TNFα) and anti-inflammatory interleukin-10 (IL-10) were also measured since changes in inflammation may contribute to UnAG activities.
CR reduced BMI and increased insulin sensitivity (p < 0.05). TotalG and UnAG but not AG increased in CR but not in Control (p < 0.05). Il-10 and IL-10/TNFα ratio also increased in CR (p < 0.05). Changes in UnAG were positively associated with changes in AUCg in all subjects (n = 20; p < 0.01) also after adjustment for treatment and changes in BMI and cytokines.
Caloric restriction modifies circulating ghrelin profile with selective increase in unacylated hormone in obese individuals. The current study supports the hypothesis that higher unacylated ghrelin contributes to improvements in insulin sensitivity following diet-induced weight loss in human obesity.
未酰化 ghrelin（UnAG）可调节胰岛素敏感性。肥胖患者血浆中 UnAG 水平降低，可能导致肥胖相关的胰岛素抵抗。我们假设，通过适度热量限制（CR）诱导肥胖人群胰岛素敏感性改善，可能与 UnAG 水平的同时升高相平行，至少部分解释了这种改善。
20 名普通社区肥胖者被随机分配到 16 周的 CR（n=11）或对照饮食（n=9）组。我们研究了 CR 对胰岛素敏感性变化（高胰岛素-正葡萄糖钳夹期间葡萄糖输注的 AUCg）与血浆总（TotalG）、酰化（AG）和未酰化 ghrelin（UnAG）之间相互作用的影响。由于炎症变化可能影响 UnAG 活性，我们还测量了血浆促炎细胞因子肿瘤坏死因子-α（TNFα）和抗炎细胞因子白细胞介素-10（IL-10）。
CR 降低了 BMI 并增加了胰岛素敏感性（p<0.05）。CR 组中 TotalG 和 UnAG 增加，但 AG 无变化，而对照组则无变化（p<0.05）。CR 组中 IL-10 和 IL-10/TNFα 比值也增加（p<0.05）。在所有受试者（n=20）中，UnAG 的变化与 AUCg 的变化呈正相关（p<0.01），即使在调整了治疗、BMI 和细胞因子的变化后也是如此。
热量限制改变了肥胖个体循环 ghrelin 谱，选择性增加了未酰化激素。本研究支持了以下假设，即较高的未酰化 ghrelin 有助于人类肥胖症中饮食诱导的体重减轻后胰岛素敏感性的改善。
