edoc

Metabolic Consequences of Adipocyte-specific Deletion of the IL-1 Receptor in Mice

Zhao, Cheng. Metabolic Consequences of Adipocyte-specific Deletion of the IL-1 Receptor in Mice. 2020, Doctoral Thesis, University of Basel, Faculty of Medicine.

[img]
Preview
PDF
2679Kb

Official URL: https://edoc.unibas.ch/76500/

Downloads: Statistics Overview

Abstract

With the increasing abundance of food and the deleterious consequences of overnutrition, metabolic stress may act on the immune system and trigger local and systemic inflammation. My host laboratory previously found that adipose tissue macrophages are the first immune cells responding to feeding after fasting by upregulating the interleukin-1 (IL-1) pathway. Therefore, we generated mice that lack the receptor for IL-1specifically in adipocytes (Il1r1fl/fl Adipoq-Cretg/0) and assessed metabolic consequences.
Despite unaltered body weight development under regular chow- and high-fat diet (HFD) feeding, we found Il1r1fl/fl Adipoq-Cretg/0 mice on chow diet to have metabolic changes indicative of pre-diabetes at 1 year of age. With HFD feeding, glucose intolerance was already apparent after 10 weeks of HFD feeding. Further, we found the gene encoding for IL-6 to be lower in adipocytes of knock out mice fed chow diet. Fluorescence-activated cell sorting (FACS) analysis revealed that the immune cell composition of the stromal vascular fraction of Il1r1fl/fl Adipoq-Cretg/0 mice are comparable to controls. Further, Il1r1fl/fl Adipoq-Cretg/0 mice pre-injected with IL-1β in a glucose tolerance test showed a blunted insulin response compared to control mice, suggesting that a part of the insulin secretagogue action of IL-1β signals via adipocytes. Interestingly, Il1r1fl/fl Adipoq-Cretg/0 mice on HFD showed an increased pancreas weight, which might point to a novel crosstalk of IL-1 signaling in fat tissue and the pancreas.
Overall, our adipocyte-specific Il1r1 knock out mice show similar body weight development as control mice but show signs of impaired glucose metabolism when aging or fed a HFD.
Advisors:Donath, Marc
Committee Members:Hess , Christoph
Faculties and Departments:03 Faculty of Medicine > Bereich Medizinische Fächer (Klinik) > Endokrinologie / Diabetologie > Endokrinologie, Diabetologie und Metabolismus (Donath)
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Medizinische Fächer (Klinik) > Endokrinologie / Diabetologie > Endokrinologie, Diabetologie und Metabolismus (Donath)
UniBasel Contributors:Hess, Christoph
Item Type:Thesis
Thesis Subtype:Doctoral Thesis
Thesis no:13582
Thesis status:Complete
Number of Pages:35
Language:English
Identification Number:
  • urn: urn:nbn:ch:bel-bau-diss135825
edoc DOI:
Last Modified:15 Feb 2022 10:58
Deposited On:01 Feb 2022 10:49

Repository Staff Only: item control page