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
{"title":"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。","authors":"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","doi":"10.1080/21623945.2022.2089394","DOIUrl":null,"url":null,"abstract":"<p><p>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.</p>","PeriodicalId":7226,"journal":{"name":"Adipocyte","volume":"11 1","pages":"366-378"},"PeriodicalIF":3.5000,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9235901/pdf/","citationCount":"1","resultStr":"{\"title\":\"Cixutumumab reveals a critical role for IGF-1 in adipose and hepatic tissue remodelling during the development of diet-induced obesity.\",\"authors\":\"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\",\"doi\":\"10.1080/21623945.2022.2089394\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>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. 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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.
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.