Inflammation in Obesity and Molecular Engineering of a Transgenic Mouse Model of Diabetes

Bibliographic Details
Main Author:	Al-Dieri, Ali Ghalib
Language:	English
Published:	University of Toledo Health Science Campus / OhioLINK 2016
Subjects:	Molecular Biology Immunology Molecular Chemistry Biochemistry Biology Pharmacy Sciences
Online Access:	http://rave.ohiolink.edu/etdc/view?acc_num=mco148131707089233

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spelling	ndltd-OhioLink-oai-etd.ohiolink.edu-mco1481317070892332021-08-03T06:39:23Z Inflammation in Obesity and Molecular Engineering of a Transgenic Mouse Model of Diabetes Al-Dieri, Ali Ghalib Molecular Biology Immunology Molecular Chemistry Biochemistry Biology Pharmacy Sciences In the first project of type 2 diabetes and obesity, we investigated the role of macrophages, adipocytes, and cytokines in diet-induced metabolic syndrome. Multiphoton microscopy of adipose tissue from obese mice detected macrophages with lipid in crown-like structures surrounding adipocytes. Macrophages expressed both TNFa and IL-10. Adipocytes occasionally expressed IL-10, but not TNFa. Adipose tissue from obese mice was digested and the adipocyte floating layer was purified. The floating layer had high mRNA levels of TNFa, but surprisingly also contained a high level of F4/80 mRNA indicating the presence of macrophages. Investigation by confocal microscopy revealed that macrophages remain adherent to adipocytes in the floating layer and contain lipids in their cytoplasm. The majority of the adherent macrophages expressed TNFa, while the adipocytes did not. Therefore, our data do not support previous reports showing TNFa expression in adipocytes. We have showed that contamination by macrophages in the purified adipocyte floating layer explains the TNFa expression.Type 1 diabetes mellitus (T1D) is an autoimmune disease that is characterized due to the destruction of the beta cells of the pancreas, by the body’s immune system. Both CD4 and CD8 T cells are required for optimal disease transfer to occur, therefore, T1D, in NOD mice, is believed to be a T cell mediated autoimmune disease due exclusively to T cells that can transfer diabetes. It has been shown that by expressing a high density of insulin receptor (IR) in their surface, chinese hamster ovary (CHO) cells could migrate toward an insulin gradient. Thus the IR is a chemotactic molecule capable of cell movement toward an insulin gradient. Our aim was to determine if a high density of IR expression is a viable mechanism to deliver T cells to the islet regardless of antigen specificity and in strains of mice that do not normally become diabetic. Therefore, in the second project of type 1 diabetes, we steered towards a Cre-Lox system with a strong CAG viral promoter and an eGFP reporter that will drive a high IR expression on all T cells. This should illustrate expression of large amounts of exogenous, tagged IR while T cells are labeled with eGFP. To this end, a viable plasmid was constructed by subcloning a mIR fragment into a lox vector with CRE recombinase restriction to ensure specific expression. 2016 English text University of Toledo Health Science Campus / OhioLINK http://rave.ohiolink.edu/etdc/view?acc_num=mco148131707089233 http://rave.ohiolink.edu/etdc/view?acc_num=mco148131707089233 unrestricted This thesis or dissertation is protected by copyright: all rights reserved. It may not be copied or redistributed beyond the terms of applicable copyright laws.
collection	NDLTD
language	English
sources	NDLTD
topic	Molecular Biology Immunology Molecular Chemistry Biochemistry Biology Pharmacy Sciences
spellingShingle	Molecular Biology Immunology Molecular Chemistry Biochemistry Biology Pharmacy Sciences Al-Dieri, Ali Ghalib Inflammation in Obesity and Molecular Engineering of a Transgenic Mouse Model of Diabetes
author	Al-Dieri, Ali Ghalib
author_facet	Al-Dieri, Ali Ghalib
author_sort	Al-Dieri, Ali Ghalib
title	Inflammation in Obesity and Molecular Engineering of a Transgenic Mouse Model of Diabetes
title_short	Inflammation in Obesity and Molecular Engineering of a Transgenic Mouse Model of Diabetes
title_full	Inflammation in Obesity and Molecular Engineering of a Transgenic Mouse Model of Diabetes
title_fullStr	Inflammation in Obesity and Molecular Engineering of a Transgenic Mouse Model of Diabetes
title_full_unstemmed	Inflammation in Obesity and Molecular Engineering of a Transgenic Mouse Model of Diabetes
title_sort	inflammation in obesity and molecular engineering of a transgenic mouse model of diabetes
publisher	University of Toledo Health Science Campus / OhioLINK
publishDate	2016
url	http://rave.ohiolink.edu/etdc/view?acc_num=mco148131707089233
work_keys_str_mv	AT aldierialighalib inflammationinobesityandmolecularengineeringofatransgenicmousemodelofdiabetes
_version_	1719440936549744640

Inflammation in Obesity and Molecular Engineering of a Transgenic Mouse Model of Diabetes

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