Furan fatty acids (FuFAs) as the active components of fish oils and omega-3 fatty acid products

Fish oilsFOand omegafatty acidswFAssuch as docosahexaenoic acidDHAand eicosapentaenoic acidEPAare some of the most prevalent natural dietary supplements used in the U Swith an estimated retail market size as high asbillion dollars annuallyAmong a variety of health benefitsit has been demonstrated that the consumption of wFAs lows the triglyceride levelsNeverthelessthe underlying mechanisms are not well established and shadowed by inconclusive and conflicting results shown in the literatureFuran fatty acidsFuFAsa class of minor natural componentswere found present in FO and wFA prescription drugsin LovazaPreliminary data has shown that FuFAs potently inhibit acetyl CoA carboxylateACCa known pharmacological target that regulates lipogenesis and lipid metabolismWe propose that FuFAs are responsible for the hypotriglyceridemic effects observed with the use FO and wFA productsFuranica has the patented synthetic approach to produce an ample supply of high purity FuFAsthe lack of which has hampered its research and development to dateThe versatile synthetic pathway will deliver a series of naturally occurring FuFAs as well as the isotopically labeled analogues for accurate quantification and animal studiesSAImprove FuFA bioanalytical tools and measure FuFA levels in commercial fish oil and wFA productsThe inconsistent results associated with wFAs might be due in part to differences in FuFA levels among various sourcesBioanalytical tools will be developed using our FuFA standards and the isotopicallylabeled analogues for the accurate measurement of FuFA levels in selected commercial productsSAEstablish the oral bioavailability of FuFAs in a rodent modelAbsolute oral bioavailability of FuFAs will be determined in a rodent model after oral gavage and IV administrations ofDone of the most common FuFAsPlasma levels ofDand its metabolite CMPFalong with their tissue distributionse gliver and pancreaswill be monitored to elucidate the role of FuFA exposure and the formation of CMPFSAReveal the direct role of FuFA in lowering triglycerides in a high fat dietHFDmouse modelDadministration in an established HFD intervention model will answer whether FuFAs dosed at levels present in wFA products are responsible for the hypotriglyceridemic effectsPlasma and hepatic triglyceride levels at the end of the study will be determined and compared with those of the controlFuFA free wFAsand CMPFOral glucose tolerance tests and insulin tolerance tests will also be performed to demonstrate the status of glucose handling at the end of the treatmentsA successful outcome of this proposal will alter the current paradigm and allow for new dietary and pharmacological approaches to managing hypertriglyceridemia to be developed involving FuFAs Hypertriglyceridemia is a condition affecting overmillion Americans and often associated with cardiovascular diseases and typediabetesWe propose to define the direct role of furan fatty acidsminor components in fish oilsregarding the hypotriglyceridemic effects associated with omegafatty acidsBoth the public and the omegaFA industry would benefit greatly from an improved understanding of beneficial components in the products