Temporal changes in soluble angiotensin-converting enzyme 2 associated with metabolic health, body composition, and proteome dynamics during a weight loss diet intervention: a randomized trial with implications for the COVID-19 pandemic.
Temporal changes in soluble angiotensin-converting enzyme 2 associated with metabolic health, body composition, and proteome dynamics during a weight loss diet intervention: a randomized trial with implications for the COVID-19 pandemic.
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DOI：
10.1093/ajcn/nqab243
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发表时间：
2021-11-08
期刊：
影响因子：
--
通讯作者：
Gardner CD
中科院分区：
文献类型：
--
作者：
Cauwenberghs N;Prunicki M;Sabovčik F;Perelman D;Contrepois K;Li X;Snyder MP;Nadeau KC;Kuznetsova T;Haddad F;Gardner CD
血管紧张素转换酶 2 (ACE2) 在代谢、心血管、肾脏和肺部疾病中发挥保护作用，并与 COVID-19 病理学相关。可溶性 ACE2 (sACE2) 随时间变化的相关性仍有待研究。我们探讨了减肥饮食干预期间 sACE2 与代谢健康和蛋白质组动态的关联。我们在 DIETFITS（检查与治疗成功相互作用的因素的饮食干预）研究中分析了 457 名 BMI 28-40 kg/m2 的健康个体（平均 ± 标准差年龄：39.8 ± 6.6 岁）。在饮食干预期间的基线和 6 个月时，通过 Olink CVDII、CVDIII 和炎症 I 阵列测量代谢健康的生化标志物和 236 种蛋白质。我们使用逐步线性回归确定了饮食引起的 sACE2 变化 (ΔsACE2) 的临床和常规生化相关性。我们结合特征选择模型和多变量调整线性回归来识别与 ΔsACE2 相关的蛋白质动力学。在饮食干预期间，sACE2 平均在 6 个月时下降。饮食干预期间 sACE2 的更强烈下降与女性性别、基线时 HOMA-IR 和 LDL 胆固醇降低以及 HOMA-IR、甘油三酯、HDL 胆固醇和脂肪量的更强烈下降独立相关。 HOMA-IR（OR：1.97；95% CI：1.28，3.03）和甘油三酯（OR：2.71；95% CI：1.72，4.26）下降的参与者在饮食干预期间 sACE2 下降的几率显着高于未进行饮食干预的参与者（P ≤ 0.0073）。特征选择模型将 ΔsACE2 与 α-1-微球蛋白/bikunin 前体、E-选择素、羟酸氧化酶 1、肾损伤分子 1、酪氨酸蛋白激酶 Mer、胎盘生长因子、血栓调节蛋白和 TNF 受体超家族成员 10B 的变化联系起来。在多变量调整线性回归中，ΔsACE2 仍然与这些蛋白质变化相关。减肥饮食干预期间 sACE2 的减少与代谢健康、脂肪量和血管紧张素肽代谢标志物、肝和血管损伤、肾功能、慢性炎症和氧化应激的改善相关。我们的研究结果可能会改善心脏代谢并发症的风险分层、预防和管理。该试验在 ClinicalTrials.gov 上注册为 NCT01826591。
Angiotensin-converting enzyme 2 (ACE2) serves protective functions in metabolic, cardiovascular, renal, and pulmonary diseases and is linked to COVID-19 pathology. The correlates of temporal changes in soluble ACE2 (sACE2) remain understudied. We explored the associations of sACE2 with metabolic health and proteome dynamics during a weight loss diet intervention. We analyzed 457 healthy individuals (mean ± SD age: 39.8 ± 6.6 y) with BMI 28–40 kg/m2 in the DIETFITS (Diet Intervention Examining the Factors Interacting with Treatment Success) study. Biochemical markers of metabolic health and 236 proteins were measured by Olink CVDII, CVDIII, and Inflammation I arrays at baseline and at 6 mo during the dietary intervention. We determined clinical and routine biochemical correlates of the diet-induced change in sACE2 (ΔsACE2) using stepwise linear regression. We combined feature selection models and multivariable-adjusted linear regression to identify protein dynamics associated with ΔsACE2. sACE2 decreased on average at 6 mo during the diet intervention. Stronger decline in sACE2 during the diet intervention was independently associated with female sex, lower HOMA-IR and LDL cholesterol at baseline, and a stronger decline in HOMA-IR, triglycerides, HDL cholesterol, and fat mass. Participants with decreasing HOMA-IR (OR: 1.97; 95% CI: 1.28, 3.03) and triglycerides (OR: 2.71; 95% CI: 1.72, 4.26) had significantly higher odds for a decrease in sACE2 during the diet intervention than those without (P ≤ 0.0073). Feature selection models linked ΔsACE2 to changes in α-1-microglobulin/bikunin precursor, E-selectin, hydroxyacid oxidase 1, kidney injury molecule 1, tyrosine-protein kinase Mer, placental growth factor, thrombomodulin, and TNF receptor superfamily member 10B. ΔsACE2 remained associated with these protein changes in multivariable-adjusted linear regression. Decrease in sACE2 during a weight loss diet intervention was associated with improvements in metabolic health, fat mass, and markers of angiotensin peptide metabolism, hepatic and vascular injury, renal function, chronic inflammation, and oxidative stress. Our findings may improve the risk stratification, prevention, and management of cardiometabolic complications. This trial was registered at clinicaltrials.gov as NCT01826591.
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