1. (+)-Z-Bisdehydrodoisynolic acid ameliorates obesity and the metabolic syndrome in female ZDF rats
- Author
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Jennifer Oitker, Yuqing Hou, Cal Y. Meyers, Nancy Henry, Jena J. Steinle, D. Allan Higginbotham, Todd A. Winters, Stuart Adler, William J. Banz, Jeremy E. Davis, and Richard G. Peterson
- Subjects
Blood Glucose ,Selective Estrogen Receptor Modulators ,medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,Medicine (miscellaneous) ,Peroxisome proliferator-activated receptor ,Gene Expression ,Kidney ,Diabetes Mellitus, Experimental ,Rosiglitazone ,chemistry.chemical_compound ,Random Allocation ,Endocrinology ,Insulin resistance ,Risk Factors ,Internal medicine ,medicine ,Animals ,Hypoglycemic Agents ,PPAR alpha ,Obesity ,Receptor ,Triglycerides ,chemistry.chemical_classification ,Metabolic Syndrome ,Cholesterol ,Body Weight ,Public Health, Environmental and Occupational Health ,Organ Size ,Phenanthrenes ,medicine.disease ,Coronary Vessels ,Rats ,Rats, Zucker ,PPAR gamma ,Disease Models, Animal ,medicine.anatomical_structure ,chemistry ,Liver ,Selective estrogen receptor modulator ,Female ,Thiazolidinediones ,Metabolic syndrome ,Food Science ,medicine.drug - Abstract
Objective: The putative selective estrogen receptor modulator (+)-Z-bisdehydrodoisynolic acid (Z-BDDA) has been found to improve cardiovascular risk in rodents. The objective of this study was to investigate the effectiveness of (+)-Z-BDDA compared with the antidiabetic drug, rosiglitazone, in treating obesity and risk factors associated with the metabolic syndrome. Research Methods and Procedures: Female Zucker Diabetic Fatty rats were randomly assigned to three treatment groups for 29 weeks: control (C), 1.8 mg (+)-Z-BDDA/kg diet [control diet + (+)-Z-BDDA (CB)], or 100 mg rosiglitazone/kg diet [control diet + rosiglitazone (CR)]. At sacrifice, physiological, biochemical, and molecular parameters were examined. Results: CB animals gained less weight and exhibited a decrease in total body lipids (p < 0.05) as compared with C or CR rats. Body weight and total body lipids were the highest in CR rats (p < 0.05). Liver weights in CB and CR rats were lower (p < 0.05) than in C rats, whereas kidney weights were lower in CB (p < 0.05) than in C and CR animals. Fasting plasma glucose was lower (p < 0.05) in the CB and CR animals when compared with C animals. C rats exhibited the highest concentration of total plasma cholesterol, and CR-treated rats exhibited the lowest concentration. Plasma triglycerides followed the same pattern as plasma cholesterol. Histomorphometry of heart vasculature revealed that CB and CR treatments produced a significant shift from small to large venules and arterioles compared with C (p < 0.05). Liver expression profiles of peroxisome proliferator-activated receptor (PPAR) α, PPARγ, and PPAR-regulated genes revealed encouraging CB-induced effects. Discussion: These results suggest that (+)-Z-BDDA may have applications in treating obesity and complications associated with the metabolic syndrome.
- Published
- 2005