Date of Degree Completion
Master of Science (MS)
Dr. Sarah Oppelt
Second Committee Member
Dr. April Binder
Third Committee Member
Dr. Carin Thomas-Bradley
Metabolic-associated fatty liver disease (MAFLD) affects 1 in 3 people in the US and is a healthcare burden on the order of billions of dollars. MAFLD is characterized by pathological lipid accumulation in the liver, excess production of triglycerides and cholesterol, and export of LDL particles that raise serum lipid levels. These metabolic perturbations can lead to the development of liver fibrosis, chronic inflammation, and insulin resistance. Diagnosing MAFLD prior to fibrosis is crucial for successful intervention and prevention of advanced liver disease and other metabolic complications. Fructose-1Phospahte (F1P) accumulation from fructose overconsumption can drive hepatic lipogenesis and MAFLD progression. Previous studies demonstrate that mice lacking the enzyme ketohexokinase, responsible for phosphorylating fructose to F1P, do not accumulate F1P and are resistant to developing MAFLD. However, common MAFLD animal models fed a fructose-rich diet take months to develop pathology. Alternatively, mice deficient in aldolase B, which cleaves F1P, will readily accumulate excess intracellular F1P and show exaggerated hepatic ballooning, macrovesicular lipid droplets, and immune cell infiltration. In this study, aldoB-/- mice, and their WT counterparts, were fed diets ranging from 0% to 0.71% fructose (w/w), for 1, 3, or 7 days, or until mice lost 20% of their initial bodyweight before fructose exposure. Histological analysis of liver tissue, quantification of total lipids, and evaluation of clinical markers of liver disease was used to characterize the development of steatosis, inflammation, and collagen deposition. We find that the aldoB-/- model develops symptoms of MAFLD without dietary fructose exposure, making it an appropriate MAFLD model. With introduction of dietary fructose, aldoB-/- mice develop more severe symptoms similar to non-alcoholic steatohepatitis (NASH), providing an inducible model for NASH. Because of this, the aldoB-/- model can aid in research about the transition between MAFLD and NASH, as well as help to identify biomarkers associated with both.
Rashid, Andy, "Characterizing cellular injury and inflammation with ALDOB-/-Mouse model of MAFLD" (2023). All Master's Theses. 1888.
Available for download on Wednesday, June 25, 2025
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