Biomarkers and Research, Nordic Bioscience, Herlev, Denmark.
KeyBioscience AG, Stans, Switzerland.
Menopause. 2021 Jan 4;28(4):423-430. doi: 10.1097/GME.0000000000001722.
Menopause is often characterized by detrimental metabolic changes, such as obesity, insulin resistance, and impaired glucose tolerance, often requiring treatment. KeyBioscience Peptides (KBPs) are Dual Amylin and Calcitonin Receptor Agonists which have shown promising metabolic effects in rats. The objective of this study was to investigate the in vivo effect of KBP on the metabolic health in a model driven by unhealthy diet, age, and menopause.
Female Sprague Dawley rats were fed a high-fat diet (HFD) for 3 months before the initiation of the study. At 6 months of age the rats were randomized into groups (n = 12) and subjected to ovariectomy surgery and treatment with KBP: (1) Lean-Sham, (2) HFD-Sham, (3) Lean-OVX, (4) HFD-OVX, (5) HFD-OVX-KBP (10 μg/kg/d), (6) HFD-OVX-KBP (20 μg/kg/d), (7) HFD-OVX-EE2 (30 μg/d 17a-ethynylestradiol). Body weight, food intake, oral glucose tolerance tests (OGTTs), subcutaneous fat, visceral fat, liver weight, and uterus weight were assessed during the 6-month study. Statistical analyses were conducted by one-way ANOVA with Tukey post-hoc test for multiple comparisons.
Combination of OVX and HFD led to significant induction of obesity (31% weight increase, P < 0.001) and insulin resistance (13% increase in tAUCglucose during OGTT P < 0.01) compared with the relevant control groups (P < 0.05), and this could be completely rescued by EE2 therapy confirming the model system (P < 0.05).Treatment of OVX-HFD rats with KBP for 26 weeks led to a significant reduction in body weight (13%, P < 0.001) in the high dose and 9% (P < 0.01) in the low dose, with corresponding improvements in fat depot sizes, all compared with HFD-OVX controls. As expected, food intake was suppressed, albeit mainly in the first 2 weeks of treatment, resulting in a reduction of overall caloric intake by 6.5% (P < 0.01) and 12.5% (P < 0.001) in the low and high doses respectively. Furthermore, treatment with KBP reduced the weight of visceral and subcutaneous fat tissues. Finally, KBP treatment significantly improved glucose tolerance, assessed using OGTTs at weeks 8, 16, and 24.
The data presented here clearly indicate a positive and sustained effect of KBP treatment on body weight loss, fat depot size, and improved glucose tolerance, illustrating the potential of KBPs as treatments for metabolic complications of overweight and menopause.
绝经通常表现为有害的代谢变化，如肥胖、胰岛素抵抗和葡萄糖耐量受损，通常需要治疗。KeyBioscience Peptides（KBPs）是双降钙素基因相关肽和胰淀素受体激动剂，在大鼠中显示出有希望的代谢效果。本研究的目的是研究 KBP 在不健康饮食、年龄和绝经驱动的模型中对代谢健康的体内影响。
雌性 Sprague Dawley 大鼠在研究开始前接受高脂肪饮食（HFD）喂养 3 个月。在 6 个月大时，大鼠被随机分为几组（n=12），并接受卵巢切除术手术和 KBP 治疗：（1）瘦 Sham，（2）HFD-Sham，（3）瘦 OVX，（4）HFD-OVX，（5）HFD-OVX-KBP（10μg/kg/d），（6）HFD-OVX-KBP（20μg/kg/d），（7）HFD-OVX-EE2（30μg/d 17a-乙炔雌二醇）。在 6 个月的研究期间，评估了体重、食物摄入量、口服葡萄糖耐量试验（OGTTs）、皮下脂肪、内脏脂肪、肝重和子宫重。通过单因素方差分析进行统计分析，并进行 Tukey 事后检验进行多重比较。
OVX 和 HFD 的组合导致肥胖（体重增加 31%，P<0.001）和胰岛素抵抗（OGTT 期间 tAUCglucose 增加 13%，P<0.01）显著诱导，与相关对照组相比（P<0.05），而 EE2 治疗完全证实了该模型系统（P<0.05）。用 KBP 治疗 26 周的 OVX-HFD 大鼠导致体重显著减轻（13%，P<0.001），高剂量组为 9%（P<0.01），相应的脂肪储存大小也有所改善，与 HFD-OVX 对照组相比均有改善。正如预期的那样，食物摄入量受到抑制，尽管主要是在治疗的前 2 周，导致低剂量和高剂量组的总热量摄入分别减少 6.5%（P<0.01）和 12.5%（P<0.001）。此外，KBP 治疗还降低了内脏和皮下脂肪组织的重量。最后，KBP 治疗显著改善了口服葡萄糖耐量试验（OGTTs）评估的葡萄糖耐量，在第 8、16 和 24 周时均有改善。
这里呈现的数据清楚地表明 KBP 治疗对体重减轻、脂肪储存大小和改善葡萄糖耐量有积极和持续的影响，这表明 KBPs 作为超重和绝经代谢并发症治疗的潜力。
