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.

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

Erratum v

Diabetologia. 2009 Jul;52(7):1455 PubMed

Zobrazit více v PubMed

J Am Diet Assoc. 2005 Mar;105(3):428-40 PubMed

Metabolism. 1996 Dec;45(12):1539-46 PubMed

Lipids. 2004 Dec;39(12):1177-85 PubMed

Crit Rev Clin Lab Sci. 2004;41(1):41-78 PubMed

Diabetes. 1999 Jan;48(1):134-40 PubMed

Am J Clin Nutr. 1999 Nov;70(5):817-25 PubMed

Am J Physiol Endocrinol Metab. 2002 Apr;282(4):E834-42 PubMed

Evid Rep Technol Assess (Summ). 2004 Mar;(89):1-4 PubMed

Am J Physiol Endocrinol Metab. 2006 Jul;291(1):E175-81 PubMed

Endocrinology. 2007 Jun;148(6):2669-80 PubMed

Diabetes Care. 2005 Jul;28(7):1547-54 PubMed

Diabetes. 2007 Apr;56(4):1034-41 PubMed

Obesity (Silver Spring). 2009 May;17(5):1023-31 PubMed

Diabetologia. 2004 Dec;47(12):2215-25 PubMed

Biochem J. 2007 Mar 15;402(3):591-600 PubMed

Int J Obes Relat Metab Disord. 1997 Aug;21(8):637-43 PubMed

Am J Physiol. 1994 Jan;266(1 Pt 1):E1-16 PubMed

Acta Physiol (Oxf). 2008 Apr;192(4):519-29 PubMed

Am J Physiol Endocrinol Metab. 2005 Jul;289(1):E30-9 PubMed

Diabetologia. 2007 Jun;50(6):1127-39 PubMed

Diabetologia. 2006 Sep;49(9):2109-19 PubMed

Obes Res. 2005 May;13(5):835-44 PubMed

Biochem Soc Trans. 2004 Feb;32(Pt 1):59-64 PubMed

J Biol Chem. 2003 Nov 14;278(46):45209-15 PubMed

J Lipid Res. 2005 Nov;46(11):2347-55 PubMed

J Clin Invest. 2004 Nov;114(9):1281-9 PubMed

PLoS One. 2008 Feb 27;3(2):e1681 PubMed

Clin Nutr. 2005 Aug;24(4):492-501 PubMed

Am J Physiol Regul Integr Comp Physiol. 2009 Jan;296(1):R57-66 PubMed

Diabetes. 2005 Dec;54(12):3358-70 PubMed

J Clin Invest. 1990 Jun;85(6):1785-92 PubMed

N Engl J Med. 2007 Jun 14;356(24):2457-71 PubMed

J Clin Invest. 1998 Mar 15;101(6):1354-61 PubMed

J Lipid Res. 2000 May;41(5):719-26 PubMed

Biochem Biophys Res Commun. 2005 Jan 28;326(4):851-8 PubMed

J Hum Nutr Diet. 2004 Oct;17(5):449-59 PubMed

Diabetologia. 2006 Feb;49(2):394-7 PubMed

Clin Sci (Lond). 2007 Jun;112(11):557-65 PubMed

Ann N Y Acad Sci. 1993 Jun 14;683:272-8 PubMed

Diabetes. 2003 Jun;52(6):1311-8 PubMed

J Biol Chem. 2004 Mar 26;279(13):12152-62 PubMed

J Clin Invest. 2007 Jun;117(6):1658-69 PubMed

J Biol Chem. 2002 Feb 15;277(7):4806-15 PubMed

Diabetologia. 2005 Nov;48(11):2365-75 PubMed

Diabetes. 1991 May;40(5):583-9 PubMed

Science. 1987 Aug 21;237(4817):885-8 PubMed

Pharmacol Ther. 2005 Jan;105(1):7-21 PubMed

Diabetes. 2005 May;54(5):1379-84 PubMed

Diabetes. 2006 Apr;55(4):924-8 PubMed

J Endocrinol Invest. 2007 Mar;30(3):210-4 PubMed

The Ameliorating Effects of n-3 Polyunsaturated Fatty Acids on Liver Steatosis Induced by a High-Fat Methionine Choline-Deficient Diet in Mice

Novel thiazolidinedione analog reduces a negative impact on bone and mesenchymal stem cell properties in obese mice compared to classical thiazolidinediones

Krill Oil Supplementation Reduces Exacerbated Hepatic Steatosis Induced by Thermoneutral Housing in Mice with Diet-Induced Obesity

Additive Effects of Omega-3 Fatty Acids and Thiazolidinediones in Mice Fed a High-Fat Diet: Triacylglycerol/Fatty Acid Cycling in Adipose Tissue

Reduced Number of Adipose Lineage and Endothelial Cells in Epididymal fat in Response to Omega-3 PUFA in Mice Fed High-Fat Diet

Plasma Acylcarnitines and Amino Acid Levels As an Early Complex Biomarker of Propensity to High-Fat Diet-Induced Obesity in Mice

Combined intervention with pioglitazone and n-3 fatty acids in metformin-treated type 2 diabetic patients: improvement of lipid metabolism

Enhancement of brown fat thermogenesis using chenodeoxycholic acid in mice

Adipose tissue-related proteins locally associated with resolution of inflammation in obese mice

Oleuropein as an inhibitor of peroxisome proliferator-activated receptor gamma

Preservation of metabolic flexibility in skeletal muscle by a combined use of n-3 PUFA and rosiglitazone in dietary obese mice

Metabolic effects of n-3 PUFA as phospholipids are superior to triglycerides in mice fed a high-fat diet: possible role of endocannabinoids

Unmasking differential effects of rosiglitazone and pioglitazone in the combination treatment with n-3 fatty acids in mice fed a high-fat diet

Synergistic induction of lipid catabolism and anti-inflammatory lipids in white fat of dietary obese mice in response to calorie restriction and n-3 fatty acids

The inhibition of fat cell proliferation by n-3 fatty acids in dietary obese mice

AMP-activated protein kinase α2 subunit is required for the preservation of hepatic insulin sensitivity by n-3 polyunsaturated fatty acids