Renal and metabolic effects of caffeine in obese (fa/fa(cp)), diabetic, hypertensive ZSF1 rats.

In Western society, the triad of hypertension, metabolic syndrome and obesity (which caries a high risk for renal disease) is increasing, as is the intake of caffeine. However, no information is available regarding the metabolic or renal consequences of caffeine consumption in this complex disease entity. The purpose of this study was to investigate the effects of chronic caffeine consumption on renal function and metabolic status in obese ZSF1 rats, an animal model of obesity, hypertension and the metabolic syndrome. Fifteen, 18-week-old male, obese ZSF1 rats were randomized to drink tap water (Cont, n = 8) or 0.1% solution of caffeine (Caff, n = 7) for 8 weeks. Metabolic and renal function measurements were performed at baseline and after 4 and 8 weeks of treatment. Caffeine treatment significantly (p < 0.05) reduced body weight, food, and fluid consumption and improved insulin sensitivity (fasting insulin 129.6+/-8.1 vs 97.5+/-3.6 microIU/mL; fed insulin 146.3+/-8.5 vs 110.6+/-3.4 microIU/mL; fasting glucose 138.7+/-13.4 vs 145+/-8.0 mg/dL; fed glucose 373+/-19.4 vs 283.3+/-19.6 mg/dL, Cont vs Caff, respectively). After 8 weeks of caffeine treatment, animals were less glycosuric as compared with control group. Area under glucose curves (AUC-glucose) in oral glucose tolerance test did not differ between the two groups (AUC- glucose: 592.5+/-42.7 vs 589.5+/-20.5 mg/dL x h, Cont vs Caff), whereas caffeine treatment significantly decreased AUC of insulin (AUC-insulin: 257.77+/-12.9 vs 198.0+/-5.9 microIU/mL x h, Cont vs. Caff, p<0.05). No differences were found with regard to plasma triglycerides and glycerol levels; however, caffeine significantly increased cholesterol levels after 4 and 8 weeks (2F-Anova, p<0.001). Moreover, caffeine significantly decreased creatinine clearance after 4 and 8 weeks (CrCl, Cont: 3.5+/-0.4, Caff: 2.2+/-0.2 L/kg/day, p<0.05) and increased protein/CrCl ratio (Cont: 323+/-30, Caff: 527+/-33 mg/L/day). Caffeine treatment for 8 weeks tended to increase plasma norepinephrine levels (p<0.06), but the two groups did not differ with regard to plasma renin activity, blood pressure, renal blood flow or and renal vascular resistance. The study indicates that caffeine improves insulin sensitivity but increases plasma cholesterol levels and impairs renal function in obesity with the metabolic syndrome and hypertension. Our results imply that the health consequences of chronic caffeine consumption may depend heavily on underlying pathophysiology process.