The Seventh Affiliated Hospital, Sun Yat-sen University, 628 Zhenyuan Road, Guangming District, Shenzhen, 518107, China; Institute of Clinical Pharmacology, Guangzhou University of Chinese Medicine, 12 Jichang Road, Baiyun District, Guangzhou, 510000, China; Guangdong Metabolic Disease Research Center of Integrated Chinese and Western Medicine, Guangzhou Higher Education Mega Center, 280 Waihuangdong Road, Guangzhou, 510008, China; The Department of Pharmacology and Clinical Pharmacology, School of Medical Sciences, Faculty of Medical and Health Sciences, University of Auckland, 85 Park Road, Grafton, Auckland, 1142, New Zealand; Centre for Brain Research, School of Medical Sciences, Faculty of Medical and Health Sciences, University of Auckland, 85 Park Road, Grafton, Auckland, 1142, New Zealand.
The Department of Pharmacology and Clinical Pharmacology, School of Medical Sciences, Faculty of Medical and Health Sciences, University of Auckland, 85 Park Road, Grafton, Auckland, 1142, New Zealand; Centre for Brain Research, School of Medical Sciences, Faculty of Medical and Health Sciences, University of Auckland, 85 Park Road, Grafton, Auckland, 1142, New Zealand; Brain Research New Zealand, A Centre of Research Excellence, New Zealand.
Nutr Metab Cardiovasc Dis. 2020 Feb 10;30(2):339-346. doi: 10.1016/j.numecd.2019.09.016. Epub 2019 Sep 25.
Insulin-like growth factor (IGF)-1 deficiency is associated with a range of metabolic disorders. Cyclic glycine-proline (cGP) is a natural nutrient and regulates the amount of active IGF-1 in plasma. Plasma cGP decreases in hypertensive women whereas increases in obese women, suggesting its involvement in cardio-metabolic function. We therefore examined the effects of cGP on metabolic profiles and blood pressure in high-fat diet (HFD)-induced obese male rats.
Male rats were fed either a HFD or a standard chow diet (STD) ad-libitum from 3 to 15 weeks of age. Rats were administered either saline or cGP from 11 to 15 weeks of age. At 14 weeks of age, systolic-blood pressure (SBP) was measured by tail-cuff plethysmography and body composition quantified by DEXA. Blood and retroperitoneal fat tissues were collected. Plasma concentrations of insulin, IGF-1, IGF binding protein (IGFBP)-3 and cGP were evaluated using ELISA and HPLC-MS respectively.
Compared to STD, HFD feeding increased SBP, total fat mass and fat/lean ratio, retroperitoneal fat weight, fasting plasma insulin and cGP concentrations whereas decreased plasma IGF-1 and IGFBP-3 concentrations. Administration of cGP reduced SBP and retroperitoneal fat weight, but had no effect on body composition and plasma insulin concentrations.
HFD-associated decreases in IGFBP-3 and increases in cGP represent an autocrine response to normalize IGF-1 function through improving the amount of bioavailable IGF-1 in the circulation of obese male rats. The beneficial effects of cGP on SBP and retroperitoneal fat mass may suggest a therapeutic potential for cGP in HFD-associated cardio-metabolic complications.
胰岛素样生长因子（IGF）-1 缺乏与多种代谢紊乱有关。循环甘氨酸-脯氨酸（cGP）是一种天然营养素，可调节血浆中活性 IGF-1 的含量。高血压女性的血浆 cGP 减少，而肥胖女性的血浆 cGP 增加，表明其参与了心脏代谢功能。因此，我们研究了 cGP 对高脂肪饮食（HFD）诱导肥胖雄性大鼠代谢谱和血压的影响。
雄性大鼠从 3 至 15 周龄时自由摄入 HFD 或标准饲料（STD）。从 11 至 15 周龄时，大鼠给予生理盐水或 cGP。在 14 周龄时，通过尾套测压法测量收缩压（SBP），并通过 DEXA 定量身体成分。采集血液和腹膜后脂肪组织。使用 ELISA 和 HPLC-MS 分别评估血浆胰岛素、IGF-1、IGF 结合蛋白（IGFBP）-3 和 cGP 的浓度。
与 STD 相比，HFD 喂养增加了 SBP、总脂肪量和脂肪/瘦肉比、腹膜后脂肪重量、空腹血浆胰岛素和 cGP 浓度，而降低了血浆 IGF-1 和 IGFBP-3 浓度。cGP 给药降低了 SBP 和腹膜后脂肪重量，但对身体成分和血浆胰岛素浓度没有影响。
HFD 相关的 IGFBP-3 减少和 cGP 增加代表了一种自分泌反应，通过改善肥胖雄性大鼠循环中生物可利用 IGF-1 的量来使 IGF-1 功能正常化。cGP 对 SBP 和腹膜后脂肪量的有益作用可能表明 cGP 在 HFD 相关心脏代谢并发症中的治疗潜力。
