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Topical Area: Dietary Bioactive Components

Dietary Bioactive Components (Poster Session)

(P03-023-23) Protective Effects of Dietary Egg Sphingomyelin in Lean and Obese NASH Mouse Models

Saturday, July 22, 2023
12:00 PM – 1:00 PM ET
Location: Poster Board 438
Disclosure(s):
Chelsea M. Garcia, M.S., B.S.: No relevant financial relationship(s) with ineligible companies to disclose.


Objectives: Nonalcoholic fatty liver disease (NAFLD) is one of the most common liver diseases and includes steatosis and non-alcoholic steatohepatitis (NASH). Over 75% of individuals with NAFLD are obese; however, those that are lean can still develop NAFLD and have limited therapeutic options. Dietary sphingomyelin is a phosphosphingolipid which has been shown to inhibit the absorption of NASH-promoting dietary lipids. The objective of this study is to investigate the effects of egg sphingomyelin (ESM) on liver injury and lipid metabolism in models of lean and obese NASH.

Methods:

Male and female C57BL/6J mice were randomized and fed a low- or high-fat diet for 9 weeks. The LFD contained 0.5% cholic acid and 2% cholesterol as a model of lean NASH (L-NASH), while the HFD contained 60% kcal from fat as a model of obese NASH (O-NASH). Diets were supplemented with either 0% or 0.1% (w/w) ESM (n = 10 mice / group / sex). As a follow up study, male C57BL/6J mice were randomized and fed the same lean and obese NASH diets for 12 weeks with either 0% or 0.3% (w/w) ESM (n = 10 mice / group). Serum/plasma and livers were collected to assess liver injury via alanine transaminase (ALT) activity and lipid profiles.

Results: Males fed 0.1% ESM had lower midpoint ALT in the L-NASH (-36%) and O-NASH (-38%) models while females fed 0.1% ESM had lower midpoint ALT (-64%) in the L-NASH model compared to controls. Mice supplemented with 0.1% ESM did not alter endpoint ALT in the O-NASH model, while 0.1% ESM reduced ALT in both female (-37%) and male (-33%) in the L-NASH model. ESM (0.1%) feeding also reduced serum total cholesterol and liver weight in L-NASH females and liver % of total body weight of O-NASH males and females. In male mice fed 0.3% ESM, ALT was reduced in both L-NASH (-55.5%) and O-NASH (-36%) groups. Lastly, 0.3% ESM reduced hepatic free cholesterol in L-NASH and reduced liver weights and hepatic total cholesterol in O-NASH mice.

Conclusions:

Low dose egg sphingomyelin supplementation protected against diet-induced liver injury as indicated by lower ALT activity in both sexes, with a greater reduction in the L-NASH model. In male mice, a higher dose of egg sphingomyelin had a protective effect in both lean and O-NASH models as shown by reduced ALT and liver cholesterol.

Funding Sources: This research was supported by USDA Hatch/Multi-State Grant to C. Blesso.