Biomedical Engineering ETDs

Publication Date

Summer 7-28-2026

Abstract

Chronic heavy metal exposures represent an underappreciated driver of metabolic dysfunction, with the liver serving as a major site of long-term accumulation for toxic metals such as cadmium. This dissertation investigates the effects of chronic, low-dose exposures of cadmium (CLEC) under normoglycemic (5.6 mM) and hyperglycemic (15 mM) exposures for 24 weeks, mimicking metabolic states relevant of healthy and type II diabetic individuals. CLEC exposure disturb glucose metabolism, elevates baseline reactive oxygen species (ROS) and impair insulin signaling via altered AKT phosphorylation and reduced IRS-2 expression. Mitochondrial dysfunction is characterized by reduced mass, increased superoxide production, loss of membrane potential, and altered oxygen consumption rates. CLEC further alter mitochondrial dynamics (fission and fusion) and lipid metabolic remodeling, supported by transcriptomic and lipidomic analyses. Notably, cell line–specific responses reveal enhanced adaptive mechanisms in HepG2 compared to HUH7 cells, potentially masking toxicity. These findings identify chronic cadmium exposure as a critical modifier of hepatic metabolic integrity and highlight CLEC as a physiologically relevant new approach methodologies (NAMs) model for long term hepatocellular dysfunction.

Language

English

Keywords

Heavy metal (Cadmium), Hyperglycemia, Metabolic disease, CLEC, Mitochondria, Insulin signaling, Lipid homeostasis

Document Type

Dissertation

Degree Name

Biomedical Engineering

Level of Degree

Doctoral

Department Name

Biomedical Engineering

First Committee Member (Chair)

Dr. Matthew J. Campen

Second Committee Member

Dr. Rama R. Gullapalli

Third Committee Member

Dr. Gabriel P. Lopez

Fourth Committee Member

Dr. Eliseo Castillo

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Available for download on Friday, July 28, 2028

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