Title

Functional Role of Lipocalin2 During The Progression of Obesity

Date of Award

6-2018

Degree Type

Thesis

Degree Name

Master of Science in Biomedical Sciences

First Advisor

Rangaiah Shashidharamurthy, PhD

Second Advisor

Avadhesh C Sharma, PharmD, PhD

Third Advisor

Valerie E Cadet, PhD

Abstract

Lipocalin2 (Lcn2) belongs to a small molecular weight lipocalin subfamily secretory proteins that binds to hydrophobic molecules. Recent studies have shown that Lcn2 highly upregulated by adipocytes and categorized as a new adipokine with a role in innate immunity and several metabolic disorders including obesity. However, the exact role Lcn2 plays in the mediation and progression of obesity has yet to be elucidated. Herein we have investigated the role of exogenous Lcn2 in inducing the beiging/browning of white adipocytes in vitro using the 3T3-Ll pre and mature murine adipocyte cell line. Treatment with exogenous recombinant Lcn2 (rLcn2) resulted in up-regulation of thermogenic and beige/brown markers (UCPI, PGCl-u, PPAR-y, PRDM16, ZIC! and TBXl). Additionally, mitochonchial activity was increased through Lcn2 exposure in 3T3-Ll cells. Further, Lcn2 treatment of pre-adipocytes resulted in attenuation of adipogenesis via the inhibition of lipid accumulation. Following ex vivo experiments, we observed that systemic as well as local Lcn2 is upregulated as the mice age. Lcn2 deficiency leads to attenuation of thermogenic and beige marker expression in an age-dependent manner. These results suggest that Lcn2 is a naturally occurring adipokine and may serve as an anti-obesity agent during the development and transdifferentiation of adipocytes and could be a potential target to attenuate and/or reverse obesity.

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