EICOSAPENTAENOIC ACID ETHYL ESTERS PREVENT OBESITY ASSOCIATED METABOLIC IMPAIRMENTS IN MALE AND FEMALE MICE

Public Deposited
Analytics

Downloadable Content

Download PDF
Request Version for Screen Reader
Creator
  • Pal, Anandita
    • Gillings School of Global Public Health, Department of Nutrition
Abstract
  • Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are omega-3 polyunsaturated fatty acids (n-3 PUFAs) that are consumed in low levels in most regions around the world. Increasing evidence suggests that pharmacological consumption of pure EPA, in particular, may prevent impairments in metabolic co-morbidities associated with obesity. However, clinical translation has been limited as several studies failed to distinguish the effect of pure EPA in comparison to crude fish oil containing DHA, sex specific effects, genetic differences, reliance on treatment as opposed to a prevention study design and limited comprehension of underlying molecular mechanisms. To address these limitations, we investigated the effects of a 60% high fat diet supplemented with pure EPA ethyl esters on male mice followed by studies on female mice. Long-term (13 week) administration of EPA in C57BL/6J male mice prevented obesity-induced hyperinsulinemia, hyperglycemia, glucose tolerance and improved the HOMA-IR score. Studies using EPA derived lipid mediator resolvin E1 (RvE1) receptor ERV1/ChemR23 knockout and wild type littermate mice revealed that RvE1 mitigated obesity induced hyperinsulinemia and hyperglycemia. Subsequent investigations in diversity outbred mice that model human genetic variation demonstrated that RvE1’s effects on fasting insulin and glucose were not uniform. Furthermore, secondary SNP analyses revealed extensive genetic variation in human RvE1- and EPA-metabolizing genes. In contrast to male C57BL/6J mice, EPA improved hyperinsulinemia and hyperglycemia, but not glucose tolerance in female mice. Based on a paucity of evidence on the microbiome in females, especially upon pure EPA administration, we investigated alterations in the microbiota composition of diet induced obese female mice. Our studies revealed a temporal shift in several phylum and lower taxonomic levels upon EPA administration. Additionally, predictive functional profiling of microbial communities revealed that EPA reversed high fat diet-associated changes in genes related to mitochondrial biogenesis, glycolysis, and gluconeogenesis, along with IL-17, NOD-like receptor and insulin signaling pathways after 6 weeks of dietary intervention. In conclusion, our findings suggest that consumption of pure EPA ethyl esters, modeling pharmacological intake, may be an effective strategy to prevent specific obesity-induced metabolic impairments mediated through distinct mechanisms.
Date of publication
Keyword
DOI
Resource type
Rights statement
  • In Copyright - Educational Use Permitted
Advisor
  • Shaikh, Saame R.
  • Adair, Linda S.
  • Beck, Melinda A.
  • Carroll, Ian
  • Coleman , Rosalind A.
Degree
  • Doctor of Philosophy
Degree granting institution
  • University of North Carolina at Chapel Hill Graduate School
Graduation year
  • 2021
Language

Relations

Parents:

This work has no parents.

Items

Thumbnail Title Date Uploaded Visibility Actions
file details Pal_unc_0153D_20166.pdf 2021-06-21 Public Download
file details Pal_unc_0153D_20166_DATA.xml 2021-06-21 Public Download