Presenter: Hannah Reichert

Authors: Hannah Reichert1, India Napier2, Amanda Armijo2, Alejandra Aguilar2, Damodaran Annamalai3, Zhongming Ge2, Yan Feng2, Claire Lyons2, Yao Lee2, Arlin Rogers4, James Fox2
1Cummings School of Veterinary Medicine at Tufts University, North Grafton, MA, USA, 2Massachusetts Institute of Technology, Cambridge, MA, USA, 3Biogen, Cambridge, MA, USA, 4Alnylam Pharmaceuticals, Cambridge, MA, USA

Background: Alcoholic liver disease (ALD) is a major cause of mortality worldwide. The L2-interleukin (IL)-1β transgenic mouse, a model of Barret’s esophagus, shows potential as an ALD model due to its persistent pro-inflammatory state. The Lieber-DeCarli (LDC) liquid diets are widely used for experimental models of ALD in rodents. More research is needed to elucidate how the liver naturally responds when L2-IL-1β mice are fed LDC diets.

Objective: Our objective was to compare the histological features of livers from male and female transgenic L2-IL-1β and littermate control (wildtype, WT) mice maintained on either standard chow or LDC diets.

Methods: Livers were collected from nine-month-old, male and female L2-IL-1β and WT mice that were exclusively fed either standard chow, or LDC diet (0.0% or 2.5% ethanol v/v) for 20 weeks. The samples were scored according to the severity of steatosis and inflammation.

Results: WT animals fed 0.0% LDC diet had higher liver inflammation and mixed steatosis scores than those maintained on standard chow (P<0.01). For both sexes fed either LDC diet, WT mice had higher mixed steatosis scores than L2-IL-1β mice (P<0.05). In WT animals, female mice fed 0.0% LDC diet and male mice fed 2.5% LDC diet had greater hepatic inflammation scores compared to their L2-IL-1β counterparts (P<0.05).

Conclusions: LDC diets cause liver inflammation and steatosis in WT animals. L2-IL-1β mice, but not WT animals, are protected against LDC diet-induced hepatocellular injury. Our findings contribute to further characterization of the L2-IL-1β transgenic mouse as a model for ALD research.

Keyword: Liver/Pancreas

Presentation Date: 11/12/22