Author ORCID Identifier

https://orcid.org/0000-0002-8640-5759

Date of Award

Spring 5-1-2023

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Biology

First Advisor

Bingzhong Xue

Second Advisor

Hang Shi

Third Advisor

Andrew Gewirtz

Abstract

2-naphthol is a low molecular weight polycyclic aromatic hydrocarbon and ubiquitous air pollutant. Recent epidemiological reports suggest that exposure to individual low molecular weight polycyclic aromatic hydrocarbons is correlated with increased incidences of childhood obesity. Yet, most studies focus on the health effects of either high molecular weight molecules or polycyclic aromatic hydrocarbon mixtures. This research explores the potential obesogenic impact of 2-naphthol in cell and animal models. To assess the in vivo effects of 2-naphthol, we monitored life fitness traits and lipid accumulation in the invertebrate Daphnia magna across development. Results showed that D. magna directly exposed to 2-naphthol demonstrated delayed reproductive development, produced fewer offspring, and accumulated more lipids than D. magna that were not exposed to 2-naphthol. Analysis of lipid accumulation by Nile Red staining revealed a dose-dependent increase in overall lipid quantity. To confirm these findings, we also examined the effect of 2-naphthol on lipid metabolism and inflammation in vitro. We employed 3T3-L1 and BAT1 mammalian cell lines to model white and brown adipocytes, respectively, alongside a murine macrophage cell line (RAW264.7). Cells were challenged with either acute or chronic 2-naphthol treatments, then differentiated adipocytes were assessed for changes in adipogenesis, lipid accumulation, and isoproterenol-stimulated thermogenesis. Additionally, LPS-induced inflammation was evaluated in both adipocytes and macrophages. 2-naphthol exposure increased the expression of key adipogenic and lipogenic genes, while lipolytic gene expression decreased in both chronically treated adipocyte lines. Further, 2-naphthol exposure suppressed isoproterenol-stimulated thermogenic gene expression in BAT1 brown adipocytes. In consistence, adipocytes exposed to 2-naphthol and stained with BODIPY and Oil Red O showed an increase in lipid accumulation. Additionally, adipocytes and macrophages chronically exposed to 2-naphthol showed an up-regulation in mRNA expression of major inflammatory cytokines, such as Tnfα, Il-1β, and Il-6. Overall, these findings support previous research that indicates 2-naphthol is a possible obesogen that may contribute to the development of obesity and associated metabolic disorders via modulating lipid metabolism and thermogenesis in adipocytes, and inflammation in both adipocytes and macrophages.

DOI

https://doi.org/10.57709/33571949

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