A Combination of CLA-DAG Oil Modifies the Diabetic Phenotype in Male Zucker Diabetic Fatty Rats

Abstract

A number of human and animal studies using conjugated linoleic acids (CLA) or diacylglycerol (DAG) oil have shown positive physiological effects on abdominal adiposity, plasma triglycerides, plasma glucose, and insulin sensitivity. A novel DAG composition containing CLA called CLA diacylglyceride (CLA-DAG) may offer potential as a therapeutic agent in reducing some of the symptoms associated with the diabetic phenotype and metabolic syndrome. This study was designed to investigate the effect of CLA-DAG oil on the diabetic phenotype in male Zucker diabetic fatty rats. Animals were assigned to one of four groups: control (C), rosiglitazone (ROS), CLA-DAG, or CLA as free fatty acid (CLA-FFA). After 11 weeks, body weight was higher and kidney weight was lower in the CLA-DAG and ROS groups compared with the C group. The ROS treatment increased the percentage of body fat as compared with all other groups. Final fasting blood glucose was lower in the CLA-DAG and ROS groups than in the C group. Plasma cholesterol was lower in the CLA-DAG group, and plasma triglycerides were lower in the ROS group compared with the C group. We also observed changes in transcript abundance of PPAR-γ, PPAR-α, FAS, LPL, UCP2, UCP3, CPT1, RxR, ObRb, ApoAII, ApoD, and IRS1 in liver, muscle, and adipose tissue, suggesting treatment-induced effects on these genes. Collectively, these data suggest the need for further research on the therapeutic relevance of CLA-DAG oil in obesity and diabetes. Future research should also differentiate between CLA alone and DAG alone compared with the combination.

Key words

transcript abundance - liver - muscle tissue - adipose tissue - metabolic syndrome

References

• 1 Taylor CG, Zahradka P. Dietary conjugated linoleic acid and insulin sensitivity and resistance in rodent models.  Am J Clin Nutr. 2004;  79 1164S-1168S
• 2 Nagao K, Yanagita T. Conjugated fatty acids in food and their health benefits.  J Biosci Bioeng. 2005;  100 152-157
• 3 Zulet MA, Marti A, Parra MD, Martinez JA. Inflammation and conjugated linoleic acid: mechanisms of action and implications for human health.  J Physiol Biochem. 2005;  61 483-494
• 4 Tricon S, Burdge GC, Jones EL, Russell JJ, El Khazen S, Moretti E, Hall WL, Gerry AB, Leake DS, Grimble RF, Williams CM, Calder PC, Yaqoob P. Effects of dairy products naturally enriched with cis-9, trans-11 conjugated linoleic acid on the blood lipid profile in healthy middle-aged men.  Am J Clin Nutr. 2006;  83 744-753
• 5 Toomey S, MacMonagle J, Roche HM. Conjugated linoleic acid: a functional nutrient in the different pathophysiological components of the metabolic syndrome?.  Curr Opin Clin Nutr Metab Care. 2006;  9 740-747
• 6 Wahle KW, Heys SD, Rotondo D. Conjugated linoleic acids: are they beneficial or detrimental to health?.  Prog Lipid Res. 2004;  43 553-587
• 7 Flickinger BD, Matsuo N. Nutritional characteristics of DAG oil.  Lipids. 2003;  38 129-132
• 8 Rudkowska I, Roynette CE, Demonty I, Vanstone CA, Jew S, Jones PJ. Diacylglycerol: efficacy and mechanism of action of an anti-obesity agent.  Obes Res. 2005;  13 1864-1876
• 9 Takase H, Shoji K, Hase T, Tokimitsu I. Effect of diacylglycerol on postprandial lipid metabolism in non-diabetic subjects with and without insulin resistance.  Atherosclerosis. 2005;  180 197-204
• 10 Nagao K, Inoue N, Wang YM, Yanagita T. Conjugated linoleic acid enhances plasma adiponectin level and alleviates hyperinsulinemia and hypertension in Zucker diabetic fatty (fa/fa) rats.  Biochem Biophys Res Commun. 2003;  310 562-566
• 11 Wendel AA, Belury MA. Effects of conjugated linoleic acid and troglitazone on lipid accumulation and composition in lean and Zucker diabetic fatty (fa/fa) rats.  Lipids. 2006;  41 241-247
• 12 Nehlin JO, Mogensen JP, Petterson I, Jeppesen L, Fleckner J, Wulff EM, Sauerberg P. Selective PPAR agonists for the treatment of type 2 diabetes.  Ann NY Acad Sci. 2006;  1067 448-453
• 13 Ramachandran U, Kumar R, Mittal A. Fine tuning of PPAR ligands for type 2 diabetes and metabolic syndrome.  Mini Rev Med Chem. 2006;  6 563-573
• 14 Zhou X, Sun C, Jiang L, Wang H. Effect of conjugated linoleic acid on PPAR gamma gene expression and serum leptin in obese rat.  Wei Sheng Yan Jiu. 2004;  33 307-309
• 15 Kang K, Liu W, Albright KJ, Park Y, Pariza MW. Trans-10,cis-12 CLA inhibits differentiation of 3T3-L1 adipocytes and decreases PPAR gamma expression.  Biochem Biophys Res Commun. 2003;  303 795-799
• 16 Moya-Camarena SY, Vanden Heuvel JP, Blanchard SG, Leesnitzer LA, Belury MA. Conjugated linoleic acid is a potent naturally occurring ligand and activator of PPARalpha.  J Lipid Res. 1999;  40 1426-1433
• 17 Davis J, Iqbal MJ, Steinle J, Oitker J, Higginbotham DA, Peterson RG, Banz WJ. Soy protein influences the development of the metabolic syndrome in male obese ZDFxSHHF rats.  Horm Metab Res. 2005;  37 316-325
• 18 Davis J, Steinle J, Higginbotham DA, Oitker J, Peterson RG, Banz WJ. Soy protein influences insulin sensitivity and cardiovascular risk in male lean SHHF rats.  Horm Metab Res. 2005;  37 309-315
• 19 Reeves PG, Nielsen FH, Fahey  Jr  GC. AIN-93 purified diets for laboratory rodents: final report of the American Institute of Nutrition ad hoc writing committee on the reformulation of the AIN-76A rodent diet.  J Nutr. 1993;  123 1939-1951
• 20 Bookout AL, Mangelsdorf DJ. Quantitative real-time PCR protocol for analysis of nuclear receptor signaling pathways.  Nucl Recept Signal. 2003;  1 e012
• 21 Banz WJ, Davis J, Peterson R, Iqbal MJ. Gene expression and adiposity are modified by soy protein in male Zucker diabetic fatty rats.  Obes Res. 2004;  12 1907-1913
• 22 Belury MA, Mahon A, Banni S. The conjugated linoleic acid (CLA) isomer, t10c12-CLA, is inversely associated with changes in body weight and serum leptin in subjects with type 2 diabetes mellitus.  J Nutr. 2003;  133 257S-260S
• 23 Shimokawa T, Kato M, Watanabe Y, Hirayama R, Kurosaki E, Shikama H, Hashimoto S. In vivo effects of pioglitazone on uncoupling protein-2 and -3 mRNA levels in skeletal muscle of hyperglycemic KK mice.  Biochem Biophys Res Commun. 1998;  251 374-378
• 24 Rassart E, Bedirian A, Do CS, Guinard O, Sirois J, Terrisse L, Milne R. Apolipoprotein D.  Biochim Biophys Acta. 2000;  1482 185-198
• 25 Wang Y, Jones PJ. Dietary conjugated linoleic acid and body composition.  Am J Clin Nutr. 2004;  79 1153S-1158S
• 26 Ryder JW, Portocarrero CP, Song XM, Cui L, Yu M, Combatsiaris T, Galuska D, Bauman DE, Barbano DM, Charron MJ, Zierath JR, Houseknecht KL. Isomer-specific antidiabetic properties of conjugated linoleic acid. Improved glucose tolerance, skeletal muscle insulin action, and UCP-2 gene expression.  Diabetes. 2001;  50 1149-1157
• 27 Song J, Knepper MA, Hu X, Verbalis JG, Ecelbarger CA. Rosiglitazone activates renal sodium- and water-reabsorptive pathways and lowers blood pressure in normal rats.  J Pharmacol Exp Ther. 2004;  308 426-433

1 Current address: The Institute for Sustainable and Renewable Resources, Institute for Advanced Learning and Research; and Department of Horticulture at Virginia Polytechnic Institute and State University, 150 Slayton Avenue, Danville, Virginia 24540; Email: [e-mail]

Correspondence