# Dietary Ethanolamine Increases Hepatic Lipid Accumulation in Mice Fed a High-Fat Diet

## TL;DR

Adding ethanolamine to a high-fat diet increases liver fat in female mice and improves glucose tolerance in males, with no direct effect on liver cells.

## Contribution

This study reveals sex-dependent effects of dietary ethanolamine on liver lipid accumulation and gut microbiota in mice.

## Key findings

- Ethanolamine increased hepatic triglycerides in female mice by 230% compared to controls.
- Male mice showed improved glucose tolerance and reduced plasma lipid levels with ethanolamine supplementation.
- Fecal microbiota diversity and early gut inflammation signals were altered in ethanolamine-fed female mice.

## Abstract

Ethanolamine (Etn), a precursor of phosphatidylethanolamine (PE), may alter hepatic lipid homeostasis and gut health; its dietary effects remain undefined.

The objective of this study was to determine the effects of dietary Etn on lipid and glucose metabolism and liver/gut health in high-fat diet (HFD)–fed mice, complemented by in vitro hepatocyte assays.

Ten-wk-old C57BL/6 mice (20 male, 18 female) were fed ad libitum HFD (45% energy from fat) with [Ethanolamine supplementation (ES-group)] or without (CON-group) Etn (8 g/kg diet) for 10 wk. Outcomes included body/liver weight, glucose tolerance test (GTT) results, plasma phosphatidylcholine (PC)/cholesteryl ester (CE)/triacylglycerol (TG) concentrations, hepatic TG/PC/PE concentrations, hepatic endoplasmic reticulum (ER)-stress, and inflammation markers, jejunal morphology/barrier/inflammation genes, and fecal microbiota (α/β diversity). HuH7 cells received 20 μM or 5 mM Etn to assess TG/PC/PE synthesis. Statistics: repeated-measures analysis of variance (ANOVA) (GTT), t-test or Wilcoxon (other endpoints), permutational multivariate analysis of variance (PERMANOVA) (β diversity); α=0.05.

ES increased hepatic TG in females by 230% compared with CON (P = 0.001), and trended higher in males (P = 0.054); hepatic PC and PE masses were unchanged. In ES males, GTT area under the curve decreased by 22.6% (P = 0.037), and plasma PC, CE, and TG were reduced by: PC −16.6%, CE −24.5%, TG −25.9%, respectively (all P < 0.05). ES males showed higher hepatic Tnf and Cd68 and increased C/EBP homologous protein (CHOP) (all P < 0.05). In vitro, Etn did not alter hepatocellular TG, PC, or PE synthesis (all P > 0.05). Female ES mice exhibited altered fecal β-diversity (PERMANOVA P = 0.006) with early jejunal inflammatory signals (Tnf ↑; P = 0.055).

Dietary Etn modifies hepatic lipid storage and gut microbiota in a sex-dependent manner and improves glucose tolerance in males, whereas in vitro data indicate no direct effect on hepatocyte lipid synthesis.