Exogenous Lipocalin2 facilitates the upregulation of thermogenic and beige/browning markers in murine white adipocytes

Abstract

Abstract Lipocalin2 (Lcn2) belongs to a small molecular weight lipocalin subfamily of secretory proteins that binds to small hydrophobic molecules. Recent studies have shown that Lcn2 is highly upregulated by adipocytes and is categorized as a new adipokine with a role in innate immunity and 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 browning of white adipocytes in vitro using the 3T3-L1 murine adipocyte cell line. Treatment with exogenous recombinant Lcn2 (rec-Lcn2) resulted in the upregulation of thermogenic and beige/brown markers (UCP1, PGC-1α, PPARγ, PRDM16, ZIC-1 and TBX1) in mature adipocytes. Additionally, rec-Lcn2 increased mitochondrial activity in 3T3-L1 cells. Further, rec-Lcn2 decreased the pre-adipocyte differentiation resulting in the attenuation of adipogenesis as evidenced by reduced lipid content accumulation. These results suggest that Lcn2 is a naturally occurring adipokine, and may serve as an anti-obesity agent by both decreasing adipogenesis in white adipocytes and inducing the transdifferentiation of white to brown-like beige adipocytes. Therefore, Lcn2 could be a potential target to attenuate/prevent obesity.