Premium
Interleukin‐1 Receptor‐1 Deficiency Impairs Metabolic Function in Pregnant and Non‐Pregnant Female Mice
Author(s) -
Plows Jasmine F,
Vickers Mark H,
Ganapathy Thashma P,
BridgeComer Pania E,
Stanley Joanna L,
Reynolds Clare M
Publication year - 2021
Publication title -
molecular nutrition and food research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.495
H-Index - 131
eISSN - 1613-4133
pISSN - 1613-4125
DOI - 10.1002/mnfr.201900770
Subject(s) - interleukin 1 receptor, type i , endocrinology , medicine , pregnancy , offspring , adipose tissue , fetus , biology , interleukin , cytokine , genetics
Scope Glucose intolerance during pregnancy is associated with short‐ and long‐term maternal and offspring health consequences. In young male mice, knockout of the major pro‐inflammatory mediator interleukin‐1‐receptor‐1 (IL1R1) protects against high‐fat diet (HFD)‐induced glucose intolerance and metabolic dysfunction. This phenotype has not been examined during pregnancy. The hypothesis that IL1R1 depletion will protect females against HFD‐induced glucose intolerance and metabolic dysfunction before, during, and post pregnancy is tested. Methods and results C57BL/6J control and IL1R1 knockout (IL1R1 −/− ) mice are randomized to either a control diet (10% kcal from fat) or HFD (45% kcal from fat), and three distinct cohorts are established: nulliparous, pregnant, and postpartum females. Contrary to the authors’ hypothesis, it is found that IL1R1 −/− does not protect against glucose intolerance in nulliparous or pregnant females, and while control HFD animals see a resolution of glucose tolerance postpartum, IL‐1R1 −/− mice remain impaired. These effects are accompanied by adipocyte hypertrophy, hyperleptinemia, and increased adipose tissue inflammatory gene expression. Maternal genotype differentially affects fetal growth in male and female fetuses, demonstrating sexual dimorphism in this genotype prior to birth. Conclusions These findings suggest that IL1R1 signaling is important for normal metabolic functioning in females, during and outside of pregnancy.