Date of Award

2021

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Graduate Group

Cell & Molecular Biology

First Advisor

Rebecca A. Simmons

Abstract

Adipose tissue has multiple functions including defense against the cold through thermogenesis of brown and beige adipocytes. The type 2 immune cytokine Interleukin-4 (IL-4) can increase beige adipogenesis in mature rodents. However, developing animals use a distinct adipocyte precursor compartment for adipogenesis compared to adults. In this body of work, we analyze the effects of IL-4 on the adipose tissue of developing rodents. In rats, we found that exogenous IL-4 induced an acute increase in beige adipogenesis and a persistent decrease in overall adipogenesis in neonatal inguinal white adipose tissue (iWAT). We determined that DPP4+ progenitors and ICAM1+ preadipocytes were the populations expressing IL-4 receptor in neonatal mice. Isolating neonatal ICAM1+ preadipocytes for RNA-seq, we discovered no significant differentially regulated genes in IL-4RKO compared to WT. After adipogenic differentiation of IL-4RKO and WT ICAM1+ preadipocytes, we also found no changes in adipocyte gene expression. However, using neonatal WT ICAM1+ preadipocytes, we show that IL-4 pretreatment increases Ucp1 expression. We also identified that IL-4 directly interferes with the process of adipogenesis, decreasing adipocyte maturation. Overall, these findings describe the role of IL-4 in developing iWAT, identify the precursor population altered by IL-4 receptor signaling and characterize long term effects of IL-4 that may influence the later onset of obesity.

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Genetics Commons

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