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减肥奇迹:新研究揭示了蛋白质卡利司他汀的惊人益处

已有 1201 次阅读 2024-5-19 19:38 |个人分类:新观察|系统分类:科普集锦

减肥奇迹:新研究揭示了蛋白质卡利司他汀的惊人益处

诸平

Young-Man-Weight-Loss-Before-After-Concept-777x518.jpg

Fig. 1 Researchers have discovered that after weight loss, individuals with overweight and obesity show increased levels of Kallistatin in their subcutaneous white adipose tissue, a protein linked to improved metabolism and potential therapeutic benefits for obesity and type 2 diabetes. This finding, explored through both clinical and animal studies, highlights Kallistatin’s role in enhancing hepatic insulin sensitivity, suggesting it as a promising target for future treatments.

Effects-of-Kallistatin-Graphic.webp.jpg

Fig. 2 Expression of the protein Kallistatin increases after weight reduction. In mice, it improves hepatic insulin sensitivity. Credit: IDMsupport@biorender.com

据德国糖尿病研究中心{German Center For Diabetes Research / Deutschen Zentrums für Diabetesforschung (DZD)}2024516日提供的消息,减肥奇迹:新研究揭示了蛋白质卡利司他汀(Protein Kallistatin)的惊人益处(Weight Loss Wonders: New Study Uncovers Surprising Benefits of the Protein Kallistatin)。

研究人员发现,体重减轻后,超重和肥胖的人皮下白色脂肪组织中的卡利司他汀水平增加,这种蛋白质与改善新陈代谢有关,对肥胖和2型糖尿病有潜在的治疗作用。这一发现,通过临床和动物研究,强调了卡利司他汀在增强肝脏胰岛素敏感性方面的作用,表明它是未来治疗的一个有希望的靶点。

新研究表明,超重个体的体重减轻会促进脂肪组织中卡利司他汀的表达,促进新陈代谢,为治疗肥胖和2型糖尿病提供了新的靶点。根据{German Center for Diabetes Research (DZD), Neuherberg, Germany}研究人员最近的一项研究,体重减轻后,超重或肥胖的人皮下白色脂肪组织中卡利司他汀蛋白水平升高。此外,卡利司他汀已被证明可以促进新陈代谢,可能为肥胖和2型糖尿病的新疗法铺平道路。研究结果于2024229日已经在《分子代谢》(Molecular Metabolism)杂志网站发表——Leontine SandforthSebastian BrachsJulia ReinkeDiana WillmesGencer SancarJudith SeignerDavid Juarez-LopezArvid SandforthJeffrey D McBrideJian-Xing MaSven HaufeJens JordanAndreas L Birkenfeld. Role of human Kallistatin in glucose and energy homeostasis in mice. Molecular Metabolism, 2024 Apr, 82: 101905. DOI: 10.1016/j.molmet.2024.101905. Epub 29 February 2024.

参与此项研究的除了来自德国多家机构的研究人员之外,还有来自美国俄克拉荷马大学健康科学中心(University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA)、美国维克森林大学医学院(Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA)以及英国伦敦国王学院(King's College London, UK)的研究人员。

越来越多的人患上2型糖尿病和肥胖症。这些都是高度复杂和多方面的疾病。为了持续治疗这些疾病,需要新的治疗方法。对人类的临床研究表明,严重超重的人产生较少的卡利司他汀。卡利司他汀是一种蛋白质,对人体有多种作用。

除此之外,它还参与对抗炎症和愈合伤口。目前,德国糖尿病研究中心(DZD)、德国图宾根大学亥姆霍兹慕尼黑糖尿病和代谢疾病研究所{Institute for Diabetes Research and Metabolic Diseases (IDM) of Helmholtz Munich at the Eberhard-Karls-University of Tübingen}以及德国图宾根大学医院糖尿病、内分泌和肾病科(Department of Diabetology, Endocrinology and Nephrology at the University Hospital Tübingen)的研究人员正在研究卡利司他汀在葡萄糖代谢中的作用及其作为治疗靶点的潜在适宜性。

减肥后卡利司他汀表达增加(Kallistatin Expression Increases After Weight Loss

为此,他们测量了47名体重超重至肥胖的人在减肥前后皮下白色脂肪组织中卡利司他汀的表达。结果:减肥后卡利司他汀表达增加。

卡利司他汀改善肝脏胰岛素敏感性(Kallistatin Improves Hepatic Insulin Sensitivity

此外,研究人员还在动物模型中检测了这种蛋白质的作用。在这个过程中,他们观察到人类的卡利司他汀可以改善饮食诱导的肥胖小鼠的肝脏胰岛素敏感性。

“我们的结果表明,对于肥胖和胰岛素抵抗的人来说,卡利司他汀可能是一个有趣的,但具有挑战性的治疗靶点,”主要作者利昂蒂内·桑德福斯(Leontine Sandforth)说。

通讯作者安德里亚斯·比肯费尔德(Andreas Birkenfeld)教授补充说:“由于卡利司他汀在肝脏中具有胰岛素致敏作用,因此应该将其作为潜在的肝脏特异性靶点进行研究,以模拟减肥的有益效果,并可能治疗2型糖尿病和肥胖。”

上述介绍,仅供参考。欲了解更多信息,敬请注意浏览原文或者相关报道

Abstract

Objective: Kallistatin (KST), also known as SERPIN A4, is a circulating, broadly acting human plasma protein with pleiotropic properties. Clinical studies in humans revealed reduced KST levels in obesity. The exact role of KST in glucose and energy homeostasis in the setting of insulin resistance and type 2 diabetes is currently unknown.

Methods: Kallistatin mRNA expression in human subcutaneous white adipose tissue (sWAT) of 47 people with overweight to obesity of the clinical trial "Comparison of Low Fat and Low Carbohydrate Diets With Respect to Weight Loss and Metabolic Effects (B-SMART)" was measured. Moreover, we studied transgenic mice systemically overexpressing human KST (hKST-TG) and wild type littermate control mice (WT) under normal chow (NCD) and high-fat diet (HFD) conditions.

Results: In sWAT of people with overweight to obesity, KST mRNA increased after diet-induced weight loss. On NCD, we did not observe differences between hKST-TG and WT mice. Under HFD conditions, body weight, body fat and liver fat content did not differ between genotypes. Yet, during intraperitoneal glucose tolerance tests (ipGTT) insulin excursions and HOMA-IR were lower in hKST-TG (4.42 ± 0.87 AU, WT vs. 2.20 ± 0.27 AU, hKST-TG, p < 0.05). Hyperinsulinemic euglycemic clamp studies with tracer-labeled glucose infusion confirmed improved insulin sensitivity by higher glucose infusion rates in hKST-TG mice (31.5 ± 1.78 mg/kg/min, hKST-TG vs. 18.1 ± 1.67 mg/kg/min, WT, p < 0.05). Improved insulin sensitivity was driven by reduced hepatic insulin resistance (clamp hepatic glucose output: 7.7 ± 1.9 mg/kg/min, hKST-TG vs 12.2 ± 0.8 mg/kg/min, WT, p < 0.05), providing evidence for direct insulin sensitizing effects of KST for the first time. Insulin sensitivity was differentially affected in skeletal muscle and adipose tissue. Mechanistically, we observed reduced Wnt signaling in the liver but not in skeletal muscle, which may explain the effect.

Conclusions: KST expression increases after weight loss in sWAT from people with obesity. Furthermore, human KST ameliorates diet-induced hepatic insulin resistance in mice, while differentially affecting skeletal muscle and adipose tissue insulin sensitivity. Thus, KST may be an interesting, yet challenging, therapeutic target for patients with obesity and insulin resistance.



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