Examination Date
Spring 2-12-2026
Degree
Dissertation
Degree Program
Physiology
Examination Committee
Liz Simon, Patricia Molina, Tekeda Ferguson, Rajani Maiya, Lisa Harrison-Bernard
Abstract
Steatotic liver disease (SLD) encompasses a spectrum of liver injury that can be driven by metabolic dysfunction, alcohol misuse, or their combination. Updated clinical nomenclature distinguishes metabolic dysfunction–associated SLD (MASLD), alcohol-associated liver disease (ALD), and the synergistic phenotype metabolic and alcohol-associated liver disease (MetALD), which carries increased risk of progression and adverse outcomes compared to MASLD. These risks are amplified in people with HIV (PWH), who experience elevated rates of metabolic dysfunction, alcohol misuse, and liver disease but remain understudied.
This dissertation details investigations of how chronic alcohol and dietary metabolic stressors interact to disrupt hepatic lipid handling, mitochondrial bioenergetics, and oxidative stress. In Simian immunodeficiency virus (SIV)-infected female macaques receiving chronic binge alcohol (CBA), data demonstrate increased molecular markers of lipid dyshomeostasis in the context of unaltered hepatic triglyceride accumulation. In male macaques fed a high‑fat, high‑sucrose diet (HFSD), SIV attenuated hepatic triglyceride content but not lipid droplet count, impaired mitochondrial pathways, and elevated markers of neutrophil infiltration. HFSD increased hepatic lipid content, and in combination with CBA, altered mitochondrial regulatory pathways and increased markers of fatty acid synthesis and oxidation.
Complementary in vitro studies using a human HepaRG hepatocyte spheroid model revealed that combined ethanol, sugar, and fat treatment produced additive disruptions in lipid storage, fatty acid oxidation markers, ATP production, and reactive oxygen species generation, recapitulating MetALD-like hepatocyte adaptations. Analysis of the New Orleans Alcohol Use in HIV (NOAH) cohort showed that in individuals with poor diet quality, alcohol misuse was associated with higher odds of liver fibrosis indices and altered liver enzymes in PWH, mirroring mechanisms identified experimentally.
Together, these findings reveal that alcohol and metabolic stressors synergistically impair hepatic lipid and mitochondrial homeostasis, with HIV/SIV conferring susceptibility through distinct mechanisms. The results identify pathways underlying MetALD with implications for targeted interventions in vulnerable populations.
Recommended Citation
Gallegos, Eden M., "INTERACTIONS OF ALCOHOL AND DIETARY METABOLIC STRESSORS ON HEPATIC LIPID AND BIOENERGETIC ADAPTATIONS: IMPLICATIONS FOR PEOPLE WITH HIV" (2026). School of Graduate Studies. 19.
https://digitalscholar.lsuhsc.edu/etd_sgs/19
Dissertation Report Form