Poster Topical Area: Energy and Macronutrient Metabolism

Location: Hall D

Poster Board Number: 495

P10-096 - EPA-derived mediators are lowered in murine obesity and rescued with dietary intervention to improve glucose clearance

Monday, Jun 11
8:00 AM – 3:00 PM

Objectives: Diet-induced obesity impairs metabolic and physiological outcomes through complex mechanisms. We explored the role of lipid mediators synthesized from polyunsaturated fatty acids (PUFA) in regulating glucose and insulin sensitivity.


Methods:We first conducted mass spectrometry analyses of specific tissues from mice consuming a high fat diet, with a focus on potential lipid mediators synthesized from n-6 and n-3 PUFAs. We subsequently assessed the potential of EPA and its metabolites in improving glucose and insulin sensitivity in mice consuming a high fat diet. 8 week old mice were fed a high fat diet or a high fat diet supplemented with 12-HEPE, 18-HEPE or EPA for 15 weeks and compared to mice on normal chow diet (CD).


Results: Select arachidonic acid derivatives were elevated in epididymal adipose tissue and liver of obese mice compared to lean controls. Notably, the hydroxylated 12-HEPE and 18-HEPE, synthesized from eicosapentaenoic acid (EPA), were dramatically lowered in adipose tissue and liver of obese mice. In contrast, 14-HDHA and 17-HDHA synthesized from docosahexaenoic acid (DHA) were not influenced by the high fat diet relative to controls. Based on these results, we tested the effects of short-term administration of 12-HEPE and 18-HEPE (4 days) in addition to long-term administration with EPA (15 weeks) on glucose clearance and fasting insulin levels. EPA, and to some extent 18-HEPE, improved fasting glucose levels and the HOMA-IR index. In addition, 18-HEPE increased in vitro force production of the skeletal muscle without affecting muscle size suggesting an improvement of muscle quality.


Conclusions: Taken together, these results suggest that EPA ethyl esters, potentially by triggering production of 18-HEPE (a pathway metabolite of resolvin E1), increase insulin-glucose sensitivity and force production in skeletal muscle.




Funding Source: The research was supported by NIH R01AT008375 (SRS), NIH R01 AR06666 (EES)

CoAuthors: William Guesdon – East Carolina University; Adam Amorese – East Carolina University; Maria J. Torres – East Carolina Diabetes and Obesity Institute, East Carolina University; P. Neufer – Department of Physiology, Brody School of Medicine, East Carolina Diabetes and Obesity Institute, East Carolina University ; Espen Spangenburg – East Carolina University; Michael Armstrong – University of Colorado-Denver ; Nichole Reisdorph – University of Colorado-Denver; Saame Shaikh – Department of Nutrition, Gillings School of Global Public Health and School of Medicine, The University of North Carolina at Chapel Hill

Anandita Pal

Graduate Research assistant
UNC Chapel Hill
Carrboro, North Carolina