AIMS/HYPOTHESIS: Fatty acids of marine origin, i.e. docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) act as hypolipidaemics, but they do not improve glycaemic control in obese and diabetic patients. Thiazolidinediones like rosiglitazone are specific activators of peroxisome proliferator-activated receptor gamma, which improve whole-body insulin sensitivity. We hypothesised that a combined treatment with a DHA and EPA concentrate (DHA/EPA) and rosiglitazone would correct, by complementary additive mechanisms, impairments of lipid and glucose homeostasis in obesity. METHODS: Male C57BL/6 mice were fed a corn oil-based high-fat diet. The effects of DHA/EPA (replacing 15% dietary lipids), rosiglitazone (10 mg/kg diet) or a combination of both on body weight, adiposity, metabolic markers and adiponectin in plasma, as well as on liver and muscle gene expression and metabolism were analysed. Euglycaemic-hyperinsulinaemic clamps were used to characterise the changes in insulin sensitivity. The effects of the treatments were also analysed in dietary obese mice with impaired glucose tolerance (IGT). RESULTS: DHA/EPA and rosiglitazone exerted additive effects in prevention of obesity, adipocyte hypertrophy, low-grade adipose tissue inflammation, dyslipidaemia and insulin resistance, while inducing adiponectin, suppressing hepatic lipogenesis and decreasing muscle ceramide concentration. The improvement in glucose tolerance reflected a synergistic stimulatory effect of the combined treatment on muscle glycogen synthesis and its sensitivity to insulin. The combination treatment also reversed dietary obesity, dyslipidaemia and IGT. CONCLUSIONS/INTERPRETATION: DHA/EPA and rosiglitazone can be used as complementary therapies to counteract dyslipidaemia and insulin resistance. The combination treatment may reduce dose requirements and hence the incidence of adverse side effects of thiazolidinedione therapy. PMID:19277604[PubMed - indexed for MEDLINE] Publication Types, MeSH Terms, SubstancesPublication TypesResearch Support, Non-U.S. Gov'tMeSH TermsAnimalsCorn Oil/pharmacologyDietary Fats/pharmacology*Docosahexaenoic Acids/pharmacologyEicosapentaenoic Acid/pharmacologyFatty Acids, Omega-3/pharmacology*Glucose Intolerance/metabolismGlycogen/biosynthesis*Hypoglycemic Agents/pharmacologyInsulin/physiology*MaleMiceMice, Inbred C57BLMuscle, Skeletal/drug effectsMuscle, Skeletal/metabolism*Thiazolidinediones/pharmacology*SubstancesDietary FatsFatty Acids, Omega-3Hypoglycemic AgentsThiazolidinedionesInsulinrosiglitazoneEicosapentaenoic AcidDocosahexaenoic AcidsCorn OilGlycogen LinkOut - more resourcesFull Text SourcesSpringerEBSCOOhioLINK Electronic Journal CenterProQuest Information and LearningSwets Information ServicesMedicalDietary Fats - MedlinePlus Health InformationDiabetes Medicines - MedlinePlus Health Information • Supplemental Content Related citations Polyunsaturated fatty acids of marine origin induce adiponectin in mice fed a high-fat diet. [Diabetologia. 2006] Polyunsaturated fatty acids of marine origin induce adiponectin in mice fed a high-fat diet. Flachs P, Mohamed-Ali V, Horakova O, Rossmeisl M, Hosseinzadeh-Attar MJ, Hensler M, Ruzickova J, Kopecky J. Diabetologia. 2006 Feb; 49(2):394-7. Epub 2006 Jan 6.Prominent role of liver in elevated plasma palmitoleate levels in response to rosiglitazone in mice fed high-fat diet. [J Physiol Pharmacol. 2009] Prominent role of liver in elevated plasma palmitoleate levels in response to rosiglitazone in mice fed high-fat diet. Kuda O, Stankova B, Tvrzicka E, Hensler M, Jelenik T, Rossmeisl M, Flachs P, Kopecky J. J Physiol Pharmacol. 2009 Dec; 60(4):135-40. Prevention and reversal of obesity and glucose intolerance in mice by DHA derivatives. [Obesity (Silver Spring). 2009] Prevention and reversal of obesity and glucose intolerance in mice by DHA derivatives. Rossmeisl M, Jelenik T, Jilkova Z, Slamova K, Kus V, Hensler M, Medrikova D, Povysil C, Flachs P, Mohamed-Ali V, et al. 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- MeSH
- Dietary Fats pharmacology MeSH
- Glycogen biosynthesis MeSH
- Hypoglycemic Agents pharmacology MeSH
- Insulin physiology MeSH
- Muscle, Skeletal metabolism drug effects MeSH
- Corn Oil pharmacology MeSH
- Eicosapentaenoic Acid pharmacology MeSH
- Docosahexaenoic Acids pharmacology MeSH
- Fatty Acids, Omega-3 pharmacology MeSH
- Mice, Inbred C57BL MeSH
- Mice MeSH
- Glucose Intolerance metabolism MeSH
- Thiazolidinediones pharmacology MeSH
- Animals MeSH
- Check Tag
- Male MeSH
- Mice MeSH
- Animals MeSH
- Publication type
- Research Support, Non-U.S. Gov't MeSH
