(+)-Z-Bisdehydrodoisynolic Acid Ameliorates Obesity and the Metabolic Syndrome in Female ZDF Rats
Article first published online: 6 SEP 2012
2005 North American Association for the Study of Obesity (NAASO)
Volume 13, Issue 11, pages 1915–1924, November 2005
How to Cite
Banz, W. J., Davis, J., Steinle, J. J., Adler, S., Oitker, J., Winters, T. A., Higginbotham, D. A., Hou, Y., Henry, N., Peterson, R. and Meyers, C. Y. (2005), (+)-Z-Bisdehydrodoisynolic Acid Ameliorates Obesity and the Metabolic Syndrome in Female ZDF Rats. Obesity Research, 13: 1915–1924. doi: 10.1038/oby.2005.236
- Issue published online: 6 SEP 2012
- Article first published online: 6 SEP 2012
- Received for review July 06, 2004; Accepted in final form August 19, 2005
- (+)-Z-bisdehydrodoisynolic acid;
- insulin resistance;
- selective estrogen receptor modulators;
- peroxisome proliferator-activated receptor;
- Zucker Diabetic Fatty rat
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.