Investigating the therapeutic potential of dietary conjugated linoleic acid (CLA) and telmisartan co-administration in metabolic syndrome in the Sprague-Dawley rat.

摘要

Metabolic syndrome (MetS) is a term linking the clinical profiles of some of the 21st Century major health problems---obesity, diabetes, and heart disease. Both dietary conjugated linoleic acid (CLA) and the angiotensin II receptor blocker (ARB) telmisartan enhance features of MetS; however, the effects of a CLA/telmisartan combination are unknown. In this 20 wk study, dietary CLA (1.0% w/w) and telmisartan (5 mg/kg body weight per day in drinking water) versus a high-carbohydrate, high-fat control diet were tested for effects on body weight, food and water intakes, lipid profiles, glucose, insulin, blood pressure, certain cytokines, and visceral fat in adult male Sprague-Dawley (SD) rats. Differences in outcomes were detected by one-way ANOVA with post-hoc Tukey tests. Animals treated with CLA/telmisartan combination exhibited significant attenuation in weight gain (550 +/- 68 g; p0.01) relative to their counterparts in either control (721 +/- 44 g), or losartan- (696 +/- 96 g), or CLA-treated (690 +/- 90 g) animals; these changes were associated with parallel reduction in visceral fat size, but similarity in food and water intakes. The diet/drug co-administration also resulted in significantly reduced serum total cholesterol (TC) (1.6 +/- 0.5 mmol/L vs. 2.4 +/- 0.3 mmol/L; p0.05), triglyceride (TG) (1.1 +/- 0.2 mmol/L vs. 3.8 +/- 0.7 mmol/L; p0.001), and glucose (6.6 +/- 0.5 mmol/L vs. 8.6 +/- 0.6 mmol/L; p0.01) concentrations in treated rats as compared to the controls. Moreover, CLA/telmisartan significantly decreased serum TC levels as compared to losartan-treated rats (p0.05), and TG levels as compared to either losartan- or CLA-treated rats (p0.05). Lower systolic blood pressure (SBP) was induced by the combination therapy when compared to placebo (121.0 +/- 13.0 mm Hg vs. 138.0 +/- 8.0 mm Hg; p0.05, respectively). Plasma insulin concentrations were reduced by the combination protocol (1.2 +/- 0.4 ng/ml vs. 2.3 +/- 0.4 ng/ml; p0.01) relative to the controls and losartan-treated rats (p0.05) whereas no notable differences in leptin levels were observed. Plasma levels of IL1-alpha and IFN-gamma were reduced by 20% and 6%, respectively, in CLA/telmisartan-treated rats when compared to the controls whereas levels of IL1-beta, IL-4, IL-6, IL-10, and TNF-alpha were increased by 28%, 55%, 36%, 75%, and 188%, respectively.; Data of this study suggest that a combination of CLA with telmisartan is (1) safe and well-tolerated in rats over 20 weeks, (2) may attenuate high body weight, reduce hyperlipidemia and hypertension, improve glucose, and normalize insulin metabolism, and thus (3) may prevent or delay onset of MetS in SD rats and improve cardiovascular risk, and (4) may represent an effective, and safe, novel approach in the management of MetS in humans. These findings should motivate future studies to investigate the mechanisms behind the observed effects of the CLA/telmisartan co-therapy.