(+)-Z-Bisdehydrodoisynolic acid ameliorates obesity and the metabolic syndrome in female ZDF rats.
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.


METHODS
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) alpha, PPARgamma, and PPAR-regulated genes revealed encouraging CB-induced effects.


CONCLUSIONS
These results suggest that (+)-Z-BDDA may have applications in treating obesity and complications associated with the metabolic syndrome.
Banz
William J
WJ
Department of Animal Science, Food, and Nutrition, Southern Illinois University, Carbondale, IL 62901-4317, USA. banz@siu.edu
Davis
Jeremy
J
Steinle
Jena J
JJ
Adler
Stuart
S
Oitker
Jennifer
J
Winters
Todd A
TA
Higginbotham
D Allan
DA
Hou
Yuqing
Y
Henry
Nancy
N
Peterson
Richard
R
Meyers
Cal Y
CY
D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D001835:Body Weight / Q000187:drug effects; D002784:Cholesterol / Q000097:blood; D003331:Coronary Vessels / Q000187:drug effects / Q000473:pathology; D003921:Diabetes Mellitus, Experimental / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007668:Kidney / Q000473:pathology; D008099:Liver / Q000737:chemistry / Q000473:pathology; D024821:Metabolic Syndrome / Q000188:drug therapy* / Q000473:pathology; D009765:Obesity / Q000188:drug therapy* / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D047493:PPAR alpha / Q000032:analysis / Q000235:genetics; D047495:PPAR gamma / Q000032:analysis / Q000235:genetics; D010616:Phenanthrenes / Q000627:therapeutic use*; D011897:Random Allocation; D051381:Rats; D011924:Rats, Zucker; D012307:Risk Factors; D000077154:Rosiglitazone; D020845:Selective Estrogen Receptor Modulators / Q000627:therapeutic use*; D045162:Thiazolidinediones / Q000627:therapeutic use; D014280:Triglycerides / Q000097:blood
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D047493:PPAR alpha; D047495:PPAR gamma; D010616:Phenanthrenes; D020845:Selective Estrogen Receptor Modulators; D045162:Thiazolidinediones; D014280:Triglycerides; C118032:bisdehydrodoisynolic acid; D000077154:Rosiglitazone; D002784:Cholesterol