The role of wnt signalling network in adipose tissue development and plasticity

Wnt信号网络在脂肪组织发育和可塑性中的作用

• 批准号: BB/E011950/1
• 负责人: Antonio Vidal-Puig
• 金额: $ 48.38万
• 依托单位: University of Cambridge
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2007
• 资助国家: 英国
• 起止时间: 2007 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FE011950%2F1
• 关键词: role; wnt; signalling; network; adipose

Obesity and diabetes are becoming increasingly prevalent in the western world. Individuals that are obese and diabetic are at high risk of dying at an early age from heart attacks. Hence, obesity and the related metabolic diseases represent a significant public health issue. The ideal strategy would be to prevent individuals from becoming obese, but it is clear that current efforts have been ineffective at curbing this epidemic. By increasing our understanding of how normal fat tissue develops and adjusts its size in response to environmental changes, we may identify more effective strategies for maintaining their health despite increased body weight. We think that adipose tissue does not have an unlimited capacity to store fat and it is when this level is surpassed that clinical problems arise. Our research aims to identify and study a group of proteins (Wnts) that are related to tissue development and alter the program of fat cell formation. These proteins can act as messengers to control the size and recruitment of new fat tissue. How these proteins bring about these changes in human fat tissue remains unclear. We have shown that key Wnt signalling molecules are co-ordinately regulated in human fat cell formation. We have also identified a human mutation in one of these molecules, in an obese individual. This mutation appears to render the molecule signalling defective and may be related to their obesity. Herein, we propose to identify and characterise the full complement of these molecules and identify their roles in altering fat tissue size in specific experimental models of obesity and fat cell development. We will also generate a new model that will allow us to investigate the role of this novel wnt mutant in whole body energy storage. We hypothesise that the wnt signalling network orchestrates the balance between fat cell recruitment and size. Alterations in this network may result in increased fat tissue size and cell number that ultimately may have important metabolic consequences.

在西方世界，肥胖和糖尿病越来越普遍。肥胖和糖尿病患者的患者在心脏病发作时有很高的死亡风险。因此，肥胖和相关的代谢疾病代表了一个重大的公共卫生问题。理想的策略是防止个人变得肥胖，但很明显，目前的努力在遏制这种流行方面一直无效。通过对正常脂肪组织如何发展并根据环境变化的响应来调整其规模，我们可以确定尽管体重增加，我们可以确定维持健康的策略。我们认为，脂肪组织没有储存脂肪的无限能力，而当超过此水平时，就会出现临床问题。我们的研究旨在鉴定和研究与组织发育相关并改变脂肪细胞形成程序的一组蛋白质（WNT）。这些蛋白质可以充当控制新脂肪组织的大小和募集的使者。这些蛋白质如何带来人类脂肪组织中的这些变化尚不清楚。我们已经表明，关键的Wnt信号分子在人脂肪细胞形成中协调调节。我们还在肥胖个体中确定了其中一个分子中的人类突变。该突变似乎使分子信号传导有缺陷，并且可能与它们的肥胖有关。在此，我们建议识别和表征这些分子的完整补体，并确定它们在肥胖和脂肪细胞发育的特定实验模型中改变脂肪组织大小中的作用。我们还将生成一个新模型，该模型将使我们能够研究这种新型Wnt突变体在全身能量存储中的作用。我们假设WNT信号网络策划了脂肪细胞募集与大小之间的平衡。该网络的改变可能会导致脂肪组织的大小和细胞数增加，最终可能会带来重要的代谢后果。

项目成果

Secreted frizzled-related protein 1 regulates adipose tissue expansion and is dysregulated in severe obesity.

• DOI: 10.1038/ijo.2010.107
• 发表时间: 2010-12
• 期刊: INTERNATIONAL JOURNAL OF OBESITY
• 影响因子: 4.9
• 作者: Lagathu, C.;Christodoulides, C.;Tan, C. Y.;Virtue, S.;Laudes, M.;Campbell, M.;Ishikawa, K.;Ortega, F.;Tinahones, F. J.;Fernandez-Real, J-M;Oresic, M.;Sethi, J. K.;Vidal-Puig, A.
• 通讯作者: Vidal-Puig, A.

Wnt signalling and the control of cellular metabolism.

• DOI: 10.1042/bj20091866
• 发表时间: 2010-03-15
• 期刊: The Biochemical journal
• 作者: Sethi JK;Vidal-Puig A
• 通讯作者: Vidal-Puig A

Adipose tissue expandability, lipotoxicity and the metabolic syndrome.

脂肪组织扩张性、脂毒性和代谢综合征。

• DOI: 10.1016/s1575-0922(13)70026-3
• 发表时间: 2013
• 期刊: organo de la Sociedad Espanola de Endocrinologia y Nutricion
• 作者: Vidal-Puig A