Inhibition of Fatty Acid Binding Protein 4 in Obese Male Mice Adversely Affects Reproductive Parameters
Tevfik Balci1, Rahim Kocabas2, Gokhan Cuce3
1Osmaniye Provincial Health Directorate, Public Health Laboratories, Osmaniye, Turkey.
Background:
As obesity is increasing worldwide, obese people use various methods to get rid of excess weight. BMS309403 (A drug) is a specific inhibitor of fatty acid binding protein 4. In this study, the effects of the BMS309403 on serum biochemical markers, testis tissue spermatogenesis and apoptotic markers were investigated in male mice.
Methods:
Balb/c mice (total=56, each group n=14) were divided into control, obese control, obese solvent and obese drug groups. The obese control, obese solvent and obese drug groups were fed on the high sucrose diet to lead to obesity. After the development of obesity, BMS309403 was orally administered to the obese drug group for six weeks. It was performed in testicular tissues (Johnson Score and apoptosis markers) and biochemical tests (total testosterone, sex hormone binding globulin, inhibin-B tests and free androgen index) were used to evaluate reproductive parameters. The p<0.05 was considered to indicate a statistical significance.
Results:
Serum fatty acid binding protein 4 levels were higher in obese control group and obese solvent group, compared to control (p<0.05) and obese drug groups (p<0.001). Serum total testosterone, free androgen index, inhibin-B, sex hormone binding globulin levels, testicular tissue B-cell lymphoma-2 expression level and Johnson Score parameters were lower in all obese groups compared with the control group. Inhibin-B levels and Johnson Score results were lower in obese drug group compared to other two obese groups (p<0.05).
Conclusion:
Contrary to expectations, the use of BMS309403 negatively affected male reproductive parameters. Negative changes in reproductive parameters may be a result of the increased lee index of obesity.
Insights
The drug BMS309403, an inhibitor of fatty acid binding protein 4, negatively impacted male reproductive health in obese mice. This study investigated its effects on testosterone and sperm parameters, revealing adverse outcomes contrary to expectations.
Area of Science:
- Endocrinology and Reproductive Biology
- Metabolic Syndrome Research
Background:
- Rising global obesity rates necessitate effective weight management strategies.
- Fatty acid binding protein 4 (FABP4) is implicated in metabolic disorders.
- BMS309403 is a specific inhibitor of FABP4, investigated for potential therapeutic effects.
Purpose of the Study:
- To evaluate the impact of BMS309403 on male reproductive parameters in an obese mouse model.
- To assess changes in serum biochemical markers, testicular spermatogenesis, and apoptotic markers following BMS309403 administration.
Main Methods:
- Balb/c mice were induced into obesity using a high-sucrose diet.
- Obese mice received oral administration of BMS309403 for six weeks.
- Reproductive parameters were assessed via serum tests (testosterone, SHBG, inhibin-B, FAI) and testicular analysis (Johnson Score, apoptosis markers).
Main Results:
- Obese groups exhibited elevated serum FABP4 levels compared to controls.
- Serum testosterone, inhibin-B, SHBG, and free androgen index were reduced in all obese groups.
- BMS309403 treatment further decreased inhibin-B levels and worsened testicular parameters (Johnson Score) in obese mice.
Conclusions:
- BMS309403 administration negatively affected male reproductive parameters in obese mice.
- The observed adverse effects may be linked to an increased obesity index.
- These findings suggest potential risks of using FABP4 inhibitors in managing obesity concerning male reproductive health.
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