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. Obesity (Silver Spring). 2009 May; 17(5):1023-31. Epub 2009 Jan 15.Review N-3 long chain polyunsaturated fatty acids: a nutritional tool to prevent insulin resistance associated to type 2 diabetes and obesity? [Reprod Nutr Dev. 2004] Review N-3 long chain polyunsaturated fatty acids: a nutritional tool to prevent insulin resistance associated to type 2 diabetes and obesity? Delarue J, LeFoll C, Corporeau C, Lucas D. Reprod Nutr Dev. 2004 May-Jun; 44(3):289-99. Review Central role of the adipocyte in the insulin-sensitising and cardiovascular risk modifying actions of the thiazolidinediones. [Biochimie. 2003] Review Central role of the adipocyte in the insulin-sensitising and cardiovascular risk modifying actions of the thiazolidinediones. Smith SA. Biochimie. 2003 Dec; 85(12):1219-30. See reviews... See all... Cited by 2 PubMed Central articles Different adipose depots: their role in the development of metabolic syndrome and mitochondrial response to hypolipidemic agents. [J Obes. 2011] Different adipose depots: their role in the development of metabolic syndrome and mitochondrial response to hypolipidemic agents. Bjorndal B, Burri L, Staalesen V, Skorve J, Berge RK. J Obes. 2011; 2011:490650. Epub 2011 Feb 15.Can vagus nerve stimulation halt or ameliorate rheumatoid arthritis and lupus? [Lipids Health Dis. 2011] Can vagus nerve stimulation halt or ameliorate rheumatoid arthritis and lupus? Das UN. Lipids Health Dis. 2011 Jan 24; 10:19. Epub 2011 Jan 24.All links from this record Related Citations Calculated set of PubMed citations closely related to the selected article(s) retrieved using a word weight algorithm. Related articles are displayed in ranked order from most to least relevant, with the “linked from” citation displayed first.Compound (MeSH Keyword) PubChem chemical compound records that are classified under the same Medical Subject Headings (MeSH) controlled vocabulary as the current articles.Substance (MeSH Keyword) PubChem chemical substance (submitted) records that are classified under the same Medical Subject Headings (MeSH) controlled vocabulary as the current articles.Cited in PMC Full-text articles in the PubMed Central Database that cite the current articles.

SourceDepartment of Adipose Tissue Biology Institute of Physiology of the Academy of Sciences of the Czech Republic Prague Czech Republic