Poster Topical Area: Energy and Macronutrient Metabolism
Location: Hall D
Poster Board Number: 495
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.
Graduate Research assistant
UNC Chapel Hill
Carrboro, North Carolina