环妥珠单抗揭示了IGF-1在饮食性肥胖发展过程中脂肪和肝组织重塑中的关键作用。

IF 3.5 4区 生物学 Q2 ENDOCRINOLOGY & METABOLISM Adipocyte Pub Date : 2022-12-01 DOI:10.1080/21623945.2022.2089394
Helen Imrie, Hema Viswambharan, Natalie J Haywood, Katherine I Bridge, Nadira Y Yuldasheva, Stacey Galloway, Katie J Simmons, Richard M Cubbon, Piruthivi Sukumar, Nicole T Watt, Laeticia Lichtenstein, Judy I Wyatt, Hiromi Kudo, Robert Goldin, Baptiste Rode, Stephen B Wheatcroft, Mark T Kearney
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引用次数: 1

摘要

高脂饮食(HFD)诱导的肥胖导致白色脂肪组织(WAT)储存功能的紊乱,导致脂肪沉积在缺乏应对这一挑战能力的组织中。胰岛素样生长因子-1 (IGF-1)在HFD的全身和器官特异性反应中的作用尚不清楚。使用环妥珠单抗,一种内化和降解细胞表面IGF-1受体(igf - 1r)的单克隆抗体,保持胰岛素受体表达不变,我们旨在确定igf - 1r在HFD应答中的作用。用环妥珠单抗治疗的小鼠以标准饲料喂养,出现轻度高胰岛素血症,WAT没有变化。接受环妥珠单抗治疗的HFD小鼠体重增加减少,WAT扩张减少,肝脂泡形成减少。在饲喂hfd的小鼠中,环妥珠单抗导致WAT和肝脏中编码脂肪酸代谢重要蛋白质的基因水平降低。环妥珠单抗对HFD喂养小鼠肝脏中胰岛素刺激的Akt磷酸化钝化具有保护作用。这些数据揭示了igf - 1r在WAT和肝脏对短期营养过剩的反应中的重要作用。在HFD期间,IGF-1 R抑制导致脂肪营养不良表型,WAT脂质储存和对HFD诱导的肝脏胰岛素抵抗的保护失败。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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Cixutumumab reveals a critical role for IGF-1 in adipose and hepatic tissue remodelling during the development of diet-induced obesity.

High fat diet (HFD)-induced obesity leads to perturbation in the storage function of white adipose tissue (WAT) resulting in deposition of lipids in tissues ill-equipped to deal with this challenge. The role of insulin like growth factor-1 (IGF-1) in the systemic and organ-specific responses to HFD is unclear. Using cixutumumab, a monoclonal antibody that internalizes and degrades cell surface IGF-1 receptors (IGF-1 R), leaving insulin receptor expression unchanged we aimed to establish the role of IGF-1 R in the response to a HFD. Mice treated with cixutumumab fed standard chow developed mild hyperinsulinemia with no change in WAT. When challenged by HFD mice treated with cixutumumab had reduced weight gain, reduced WAT expansion, and reduced hepatic lipid vacuole formation. In HFD-fed mice, cixutumumab led to reduced levels of genes encoding proteins important in fatty acid metabolism in WAT and liver. Cixutumumab protected against blunting of insulin-stimulated phosphorylation of Akt in liver of HFD fed mice. These data reveal an important role for IGF-1 R in the WAT and hepatic response to short-term nutrient excess. IGF-1 R inhibition during HFD leads to a lipodystrophic phenotype with a failure of WAT lipid storage and protection from HFD-induced hepatic insulin resistance.

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来源期刊
Adipocyte
Adipocyte Medicine-Histology
CiteScore
6.50
自引率
3.00%
发文量
46
审稿时长
32 weeks
期刊介绍: Adipocyte recognizes that the adipose tissue is the largest endocrine organ in the body, and explores the link between dysfunctional adipose tissue and the growing number of chronic diseases including diabetes, hypertension, cardiovascular disease and cancer. Historically, the primary function of the adipose tissue was limited to energy storage and thermoregulation. However, a plethora of research over the past 3 decades has recognized the dynamic role of the adipose tissue and its contribution to a variety of physiological processes including reproduction, angiogenesis, apoptosis, inflammation, blood pressure, coagulation, fibrinolysis, immunity and general metabolic homeostasis. The field of Adipose Tissue research has grown tremendously, and Adipocyte is the first international peer-reviewed journal of its kind providing a multi-disciplinary forum for research focusing exclusively on all aspects of adipose tissue physiology and pathophysiology. Adipocyte accepts high-profile submissions in basic, translational and clinical research.
期刊最新文献
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