Conclusions
The data presented here clearly indicate a positive and sustained effect of KBP treatment on body weight loss, fat depot size, and improved glucose tolerance, illustrating the potential of KBPs as treatments for metabolic complications of overweight and menopause.
Methods
Female Sprague Dawley rats were fed a high-fat diet (HFD) for 3 months before the initiation of the study. At 6 months of age the rats were randomized into groups (n = 12) and subjected to ovariectomy surgery and treatment with KBP: (1) Lean-Sham, (2) HFD-Sham, (3) Lean-OVX, (4) HFD-OVX, (5) HFD-OVX-KBP (10 μg/kg/d), (6) HFD-OVX-KBP (20 μg/kg/d), (7) HFD-OVX-EE2 (30 μg/d 17a-ethynylestradiol). Body weight, food intake, oral glucose tolerance tests (OGTTs), subcutaneous fat, visceral fat, liver weight, and uterus weight were assessed during the 6-month study. Statistical analyses were conducted by one-way ANOVA with Tukey post-hoc test for multiple comparisons.
Results
Combination of OVX and HFD led to significant induction of obesity (31% weight increase, P < 0.001) and insulin resistance (13% increase in tAUCglucose during OGTT P < 0.01) compared with the relevant control groups (P < 0.05), and this could be completely rescued by EE2 therapy confirming the model system (P < 0.05).Treatment of OVX-HFD rats with KBP for 26 weeks led to a significant reduction in body weight (13%, P < 0.001) in the high dose and 9% (P < 0.01) in the low dose, with corresponding improvements in fat depot sizes, all compared with HFD-OVX controls. As expected, food intake was suppressed, albeit mainly in the first 2 weeks of treatment, resulting in a reduction of overall caloric intake by 6.5% (P < 0.01) and 12.5% (P < 0.001) in the low and high doses respectively. Furthermore, treatment with KBP reduced the weight of visceral and subcutaneous fat tissues. Finally, KBP treatment significantly improved glucose tolerance, assessed using OGTTs at weeks 8, 16, and 24. Conclusions: The data presented here clearly indicate a positive and sustained effect of KBP treatment on body weight loss, fat depot size, and improved glucose tolerance, illustrating the potential of KBPs as treatments for metabolic complications of overweight and menopause.