PreprintArticleVersion 1Preserved in Portico This version is not peer-reviewed
A Mouse Model of Low Adipocyte Transferrin Recapitulates the Phenotype of a Human Genetic Polymorphism Associated with Insulin Sensitivity and Transferrin Expression
Version 1
: Received: 26 August 2023 / Approved: 30 August 2023 / Online: 31 August 2023 (07:14:33 CEST)
How to cite:
Lorenzo, F.R.; Das, S.K.; Harrison, A.V.; Sink, S.; McClain, D.A. A Mouse Model of Low Adipocyte Transferrin Recapitulates the Phenotype of a Human Genetic Polymorphism Associated with Insulin Sensitivity and Transferrin Expression. Preprints2023, 2023082142. https://doi.org/10.20944/preprints202308.2142.v1
Lorenzo, F.R.; Das, S.K.; Harrison, A.V.; Sink, S.; McClain, D.A. A Mouse Model of Low Adipocyte Transferrin Recapitulates the Phenotype of a Human Genetic Polymorphism Associated with Insulin Sensitivity and Transferrin Expression. Preprints 2023, 2023082142. https://doi.org/10.20944/preprints202308.2142.v1
Lorenzo, F.R.; Das, S.K.; Harrison, A.V.; Sink, S.; McClain, D.A. A Mouse Model of Low Adipocyte Transferrin Recapitulates the Phenotype of a Human Genetic Polymorphism Associated with Insulin Sensitivity and Transferrin Expression. Preprints2023, 2023082142. https://doi.org/10.20944/preprints202308.2142.v1
APA Style
Lorenzo, F.R., Das, S.K., Harrison, A.V., Sink, S., & McClain, D.A. (2023). A Mouse Model of Low Adipocyte Transferrin Recapitulates the Phenotype of a Human Genetic Polymorphism Associated with Insulin Sensitivity and Transferrin Expression. Preprints. https://doi.org/10.20944/preprints202308.2142.v1
Chicago/Turabian Style
Lorenzo, F.R., Sandy Sink and Donald A McClain. 2023 "A Mouse Model of Low Adipocyte Transferrin Recapitulates the Phenotype of a Human Genetic Polymorphism Associated with Insulin Sensitivity and Transferrin Expression" Preprints. https://doi.org/10.20944/preprints202308.2142.v1
Abstract
Transferrin (TF) is a key iron carrier protein. Studies in human cohorts and in cultured adipocytes suggested that decreased transferrin expression and intracellular iron in adipocytes leads to impaired insulin responsiveness and causes differential expression of genes involved in metabolism, insulin action, and obesity. While suggestive, these studies did not definitively prove in an intact organism that altering TF expression in adipocytes is sufficient to affect glucose homeostasis and insulin resistance. In this study we created a mouse model of decreased transferrin expression only in adipocytes (Trf+/-Cre+/-) to test the hypothesis that iron trafficking in adipose tissue is sufficient to affect insulin sensitivity. Area under the glucose curve (AUCg) after intraperitoneal glucose administration was increased in the Trf+/-Cre+/- mice compared to wild type (WT) mice on a normal chow diet, and the mice were slightly heavier (p=0.02 for both). Homeostasis Model of Insulin Resistance (HOMA-IR) values were also significantly higher in the Trf+/- Cre+/- mice (p<0.05). Thus, supporting our hypothesis, analysis of mice with decreased expression of TF restricted to adipocytes showed that a decrease in adipocyte TF is sufficient to affect insulin resistance, weight, and glucose homeostasis.
Keywords
Transferrin; Iron; Adipocyte; Insulin Resistance; Type 2 Diabetes Mellitus
Subject
Medicine and Pharmacology, Endocrinology and Metabolism
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
