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Supplementation with EPA or fish oil for 11 months lowers circulating lipids, but does not delay the onset of diabetes in UC Davis-type 2 diabetes mellitus rats

  • Bethany P. Cummings (a1) (a2), Kimber L. Stanhope (a1) (a2), James L. Graham (a1) (a2), Steven C. Griffen (a3) and Peter J. Havel (a1) (a2)...

EPA or fish oil supplementation has been suggested as treatments for the prevention of type 2 diabetes mellitus (T2DM) due to their lipid-lowering and potential insulin-sensitising effects. We investigated the effects of supplementation with EPA (1 g/kg body weight per d) or fish oil (3 g/kg body weight per d) on the age of onset of T2DM and circulating glucose, insulin, lipids, leptin and adiponectin in UC Davis (UCD)-T2DM rats. Animals were divided into three groups starting at 1 month of age: control, EPA and fish oil. All the animals were followed until diabetes onset or for up to 12 months of age. Monthly fasting blood samples were collected for the measurement of glucose, lipids, hormones and C-reactive protein (CRP). Neither EPA nor fish oil delayed the onset of T2DM or altered fasting plasma glucose, insulin, CRP, adiponectin or leptin concentrations. The groups did not differ in energy intake or body weight. Fish oil treatment lowered fasting plasma TAG concentrations by 39 (sd 7) % (P < 0·001) and EPA lowered fasting plasma NEFA concentrations by 23 (sd 5) % (P < 0·05) at 4 months of age compared with the control group. EPA and fish oil lowered fasting plasma cholesterol concentrations at 4 months of age by 19 (sd 4) and 22 (sd 4) % compared with the control group, respectively (both P < 0·01). In conclusion, EPA and fish oil supplementation lowers circulating lipid concentrations, but does not delay the onset of T2DM in UCD-T2DM rats.

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      Supplementation with EPA or fish oil for 11 months lowers circulating lipids, but does not delay the onset of diabetes in UC Davis-type 2 diabetes mellitus rats
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      Supplementation with EPA or fish oil for 11 months lowers circulating lipids, but does not delay the onset of diabetes in UC Davis-type 2 diabetes mellitus rats
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      Supplementation with EPA or fish oil for 11 months lowers circulating lipids, but does not delay the onset of diabetes in UC Davis-type 2 diabetes mellitus rats
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Corresponding author
*Corresponding author: P. J. Havel, fax +1 530 752 4698, email
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1 Calder PC (2002) Dietary modification of inflammation with lipids. Proc Nutr Soc 61, 345358.
2 Li H, Ruan XZ, Powis SH, et al. (2005) EPA and DHA reduce LPS-induced inflammation responses in HK-2 cells: evidence for a PPAR-gamma-dependent mechanism. Kidney Int 67, 867874.
3 Itoh M, Suganami T, Satoh N, et al. (2007) Increased adiponectin secretion by highly purified eicosapentaenoic acid in rodent models of obesity and human obese subjects. Arterioscler Thromb Vasc Biol 27, 19181925.
4 Kabir M, Skurnik G, Naour N, et al. (2007) Treatment for 2 mo with n 3 polyunsaturated fatty acids reduces adiposity and some atherogenic factors but does not improve insulin sensitivity in women with type 2 diabetes: a randomized controlled study. Am J Clin Nutr 86, 16701679.
5 Perez-Matute P, Perez-Echarri N, Martinez JA, et al. (2007) Eicosapentaenoic acid actions on adiposity and insulin resistance in control and high-fat-fed rats: role of apoptosis, adiponectin and tumour necrosis factor-alpha. Br J Nutr 97, 389398.
6 Grimsgaard S, Bonaa KH, Hansen JB, et al. (1997) Highly purified eicosapentaenoic acid and docosahexaenoic acid in humans have similar triacylglycerol-lowering effects but divergent effects on serum fatty acids. Am J Clin Nutr 66, 649659.
7 Woodman RJ, Mori TA, Burke V, et al. (2002) Effects of purified eicosapentaenoic and docosahexaenoic acids on glycemic control, blood pressure, and serum lipids in type 2 diabetic patients with treated hypertension. Am J Clin Nutr 76, 10071015.
8 Davidson MH (2006) Mechanisms for the hypotriglyceridemic effect of marine omega-3 fatty acids. Am J Cardiol 98, 27i33i.
9 Yokoyama M, Origasa H, Matsuzaki M, et al. (2007) Effects of eicosapentaenoic acid on major coronary events in hypercholesterolaemic patients (JELIS): a randomised open-label, blinded endpoint analysis. Lancet 369, 10901098.
10 Storlien LH, Baur LA, Kriketos AD, et al. (1996) Dietary fats and insulin action. Diabetologia 39, 621631.
11 Rossi AS, Lombardo YB, Lacorte JM, et al. (2005) Dietary fish oil positively regulates plasma leptin and adiponectin levels in sucrose-fed, insulin-resistant rats. Am J Physiol Regul Integr Comp Physiol 289, R486R494.
12 Jump DB (2002) The biochemistry of n-3 polyunsaturated fatty acids. J Biol Chem 277, 87558758.
13 Plutzky J (2003) The potential role of peroxisome proliferator-activated receptors on inflammation in type 2 diabetes mellitus and atherosclerosis. Am J Cardiol 92, 34J41J.
14 Zhao Y, Joshi-Barve S, Barve S, et al. (2004) Eicosapentaenoic acid prevents LPS-induced TNF-alpha expression by preventing NF-kappaB activation. J Am Coll Nutr 23, 7178.
15 Ziouzenkova O & Plutzky J (2004) Lipolytic PPAR activation: new insights into the intersection of triglycerides and inflammation? Curr Opin Clin Nutr Metab Care 7, 369375.
16 Yudkin JS, Stehouwer CD, Emeis JJ, et al. (1999) C-reactive protein in healthy subjects: associations with obesity, insulin resistance, and endothelial dysfunction: a potential role for cytokines originating from adipose tissue? Arterioscler Thromb Vasc Biol 19, 972978.
17 Tataranni PA & Ortega E (2005) A burning question: does an adipokine-induced activation of the immune system mediate the effect of overnutrition on type 2 diabetes? Diabetes 54, 917927.
18 Mori TA, Burke V, Puddey IB, et al. (2000) Purified eicosapentaenoic and docosahexaenoic acids have differential effects on serum lipids and lipoproteins, LDL particle size, glucose, and insulin in mildly hyperlipidemic men. Am J Clin Nutr 71, 10851094.
19 Havel PJ (2004) Update on adipocyte hormones: regulation of energy balance and carbohydrate/lipid metabolism. Diabetes 53, Suppl. 1, S143S151.
20 Neschen S, Morino K, Rossbacher JC, et al. (2006) Fish oil regulates adiponectin secretion by a peroxisome proliferator-activated receptor-gamma-dependent mechanism in mice. Diabetes 55, 924928.
21 Semple RK, Chatterjee VK & O'Rahilly S (2006) PPAR gamma and human metabolic disease. J Clin Invest 116, 581589.
22 D'Alessandro ME, Lombardo YB & Chicco A (2002) Effect of dietary fish oil on insulin sensitivity and metabolic fate of glucose in the skeletal muscle of normal rats. Ann Nutr Metab 46, 114120.
23 Holness MJ, Greenwood GK, Smith ND, et al. (2003) Diabetogenic impact of long-chain omega-3 fatty acids on pancreatic beta-cell function and the regulation of endogenous glucose production. Endocrinology 144, 39583968.
24 Holness MJ, Smith ND, Greenwood GK, et al. (2004) Acute omega-3 fatty acid enrichment selectively reverses high-saturated fat feeding-induced insulin hypersecretion but does not improve peripheral insulin resistance. Diabetes 53, Suppl. 1, S166S171.
25 Montori VM, Farmer A, Wollan PC, et al. (2000) Fish oil supplementation in type 2 diabetes: a quantitative systematic review. Diabetes Care 23, 14071415.
26 Faeh D, Minehira K, Schwarz JM, et al. (2005) Effect of fructose overfeeding and fish oil administration on hepatic de novo lipogenesis and insulin sensitivity in healthy men. Diabetes 54, 19071913.
27 Mostad IL, Bjerve KS, Bjorgaas MR, et al. (2006) Effects of n-3 fatty acids in subjects with type 2 diabetes: reduction of insulin sensitivity and time-dependent alteration from carbohydrate to fat oxidation. Am J Clin Nutr 84, 540550.
28 Cummings BP, Digitale EK, Stanhope KL, et al. (2008) Development and characterization of a novel rat model of type 2 diabetes mellitus: the UC Davis type 2 diabetes mellitus UCD-T2DM rat. Am J Physiol Regul Integr Comp Physiol 295, R1782R1793.
29 Stanhope KL, Kras KM & Moreno-Aliaga MJ (2000) A comparison of adipocyte size and metabolism in Charles River and Harlan Sprague Dawley rats (Abstract). Obes Res 8, 66S.
30 Stanhope KL, Sinha M, Graham J, et al. (2002) Low circulating adiponectin levels and reduced adipocyte adiponectin production in obese, insulin-resistant Sprague–Dawley rats (Abstract). Diabetes 52, A404.
31 Griffen SC, Wang J & German MS (2001) A genetic defect in beta-cell gene expression segregates independently from the fa locus in the ZDF rat. Diabetes 50, 6368.
32 Bergeron R, Yao J, Woods JW, et al. (2006) Peroxisome proliferator-activated receptor (PPAR)-alpha agonism prevents the onset of type 2 diabetes in Zucker diabetic fatty rats: a comparison with PPAR gamma agonism. Endocrinology 147, 42524262.
33 Yaqoob P & Calder P (1995) Effects of dietary lipid manipulation upon inflammatory mediator production by murine macrophages. Cell Immunol 163, 120128.
34 Raclot T, Groscolas R, Langin D, et al. (1997) Site-specific regulation of gene expression by n-3 polyunsaturated fatty acids in rat white adipose tissues. J Lipid Res 38, 19631972.
35 Reseland JE, Haugen F, Hollung K, et al. (2001) Reduction of leptin gene expression by dietary polyunsaturated fatty acids. J Lipid Res 42, 743750.
36 Neschen S, Morino K, Dong J, et al. (2007) n-3 Fatty acids preserve insulin sensitivity in vivo in a peroxisome proliferator-activated receptor-alpha-dependent manner. Diabetes 56, 10341041.
37 Annuzzi G, Rivellese A, Capaldo B, et al. (1991) A controlled study on the effects of n-3 fatty acids on lipid and glucose metabolism in non-insulin-dependent diabetic patients. Atherosclerosis 87, 6573.
38 Vessby B & Boberg M (1990) Dietary supplementation with n-3 fatty acids may impair glucose homeostasis in patients with non-insulin-dependent diabetes mellitus. J Intern Med 228, 165171.
39 Vessby B, Karlstrom B, Boberg M, et al. (1992) Polyunsaturated fatty acids may impair blood glucose control in type 2 diabetic patients. Diabet Med 9, 126133.
40 Dunstan DW, Mori TA, Puddey IB, et al. (1997) The independent and combined effects of aerobic exercise and dietary fish intake on serum lipids and glycemic control in NIDDM. A randomized controlled study. Diabetes Care 20, 913921.
41 Randle PJ (1998) Regulatory interactions between lipids and carbohydrates: the glucose fatty acid cycle after 35 years. Diabetes Metab Rev 14, 263283.
42 Pawar A, Botolin D, Mangelsdorf DJ, et al. (2003) The role of liver X receptor-alpha in the fatty acid regulation of hepatic gene expression. J Biol Chem 278, 4073640743.
43 Berge RK, Madsen L, Vaagenes H, et al. (1999) In contrast with docosahexaenoic acid, eicosapentaenoic acid and hypolipidaemic derivatives decrease hepatic synthesis and secretion of Triacylglycerol by decreased diacylglycerol acyltransferase activity and stimulation of fatty acid oxidation. Biochem J Pt 1, 343, 191197.
44 Blaschke F, Takata Y, Caglayan E, et al. (2006) Obesity, peroxisome proliferator-activated receptor, and atherosclerosis in type 2 diabetes. Arterioscler Thromb Vasc Biol 26, 2840.
45 Pegorier JP, Le May C & Girard J (2004) Control of gene expression by fatty acids. J Nutr 134, 2444S2449S.
46 Long YC & Zierath JR (2006) AMP-activated protein kinase signaling in metabolic regulation. J Clin Invest 116, 17761783.
47 Lara JJ, Economou M, Wallace AM, et al. (2007) Benefits of salmon eating on traditional and novel vascular risk factors in young, non-obese healthy subjects. Atherosclerosis 193, 213221.
48 Kratz M, Swarbrick MM, Callahan HS, et al. (2008) Effect of dietary n-3 polyunsaturated fatty acids on plasma total and high-molecular-weight adiponectin concentrations in overweight to moderately obese men and women. Am J Clin Nutr 87, 347353.
49 Gillam M, Noto A, Zahradka P, et al. (2009) Improved n-3 fatty acid status does not modulate insulin resistance in fa/fa Zucker rats. Prostaglandins Leukot Essent Fatty Acids 81, 331339.
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British Journal of Nutrition
  • ISSN: 0007-1145
  • EISSN: 1475-2662
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