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Orlistat attenuates obesity-induced decline in steroidogenesis and spermatogenesis by up-regulating steroidogenic
Joseph Bagi Suleiman1,2, Victor Udo Nna3, Zaidatul Akmal Othman1,4
1Department of Physiology, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, Kelantan, Malaysia.
Background:
Steroidogenesis decline is reported to be one of the mechanisms associated with obesity-induced male factor subfertility/infertility.
Objectives:
We explored the possible preventive/therapeutic effects of orlistat (a medication prescribed for weight loss) on obesity-induced steroidogenesis and spermatogenesis decline.
Materials And Methods:
Twenty-four adult male Sprague Dawley rats weighing 250-300 g were randomized into four groups (n = 6/group), namely; normal control, high-fat diet, high-fat diet plus orlistat preventive group and high-fat diet plus orlistat treatment group. Orlistat (10 mg/kg/b.w./d suspended in distilled water) was either concurrently administered with high-fat diet for 12 weeks (high-fat diet plus orlistat preventive group) or administered from week 7-12 post- high-fat diet feeding (high-fat diet plus orlistat treatment group). Thereafter, serum, testes and epididymis were collected for analyses.
Results:
Obesity increased serum leptin and decreased adiponectin levels, decreased serum and intra-testicular levels of follicle stimulating hormone, luteinising hormone and testosterone, sperm count, motility, viability, normal morphology and epididymal antioxidants, but increased epididymal malondialdehyde level and sperm nDNA fragmentation. Testicular mRNA transcript levels of androgen receptor, luteinizing hormone receptor, steroidogenic acute regulatory protein, cytochrome P450 enzyme (CYP11A1), 3β-hydroxysteroid dehydrogenase and 17β-hydroxysteroid dehydrogenase were significantly decreased in the testes of the high-fat diet group. Further, the levels of steroidogenic acute regulatory protein protein and enzymatic activities of CYP11A1, 3β-hydroxysteroid dehydrogenase and 17β-hydroxysteroid dehydrogenase were also significantly decreased in the testes of the high-fat diet group. Treatment with orlistat significantly decreased leptin and increased adiponectin levels, improved sperm parameters, decreased sperm DNA fragmentation, increased the levels of steroidogenic hormones, proteins and associated genes in high-fat diet-induced obese male rats, with the preventive group (high-fat diet plus orlistat preventive group) having better results relative to the treatment group (high-fat diet plus orlistat treatment group).
Discussion And Conclusion:
Orlistat attenuated impaired spermatogenesis and steroidogenesis decline by up-regulating steroidogenic genes. This may not be unconnected to its significant effect in lowering serum leptin levels, since the hormone is known to dampen fertility potential. Therefore, orlistat may improve fertility potential in overweight/obese men.
Insights
Orlistat improved male fertility in obese rats by enhancing steroidogenesis and spermatogenesis. This weight loss drug counteracted obesity-induced declines in hormone levels and sperm quality, offering potential benefits for overweight men.
Area of Science:
- Reproductive Endocrinology
- Obesity Research
- Pharmacology
Background:
- Obesity is linked to male infertility through impaired steroidogenesis.
- Understanding the mechanisms of obesity-induced male subfertility is crucial for developing interventions.
Purpose of the Study:
- To investigate the preventive and therapeutic effects of orlistat on obesity-induced declines in steroidogenesis and spermatogenesis.
- To evaluate orlistat's impact on hormonal profiles, sperm parameters, and related gene expression in obese male rats.
Main Methods:
- Adult male Sprague Dawley rats were fed a high-fat diet and treated with orlistat (preventive or treatment groups) or placebo.
- Serum, testes, and epididymis were analyzed for hormonal levels, sperm parameters, oxidative stress markers, and gene/protein expression of steroidogenic enzymes.
Main Results:
- Obesity significantly decreased testosterone, LH, FSH, sperm quality, and steroidogenic gene/protein expression while increasing leptin and oxidative stress.
- Orlistat treatment (especially preventive) reversed these effects, improving hormonal balance, sperm parameters, and upregulating key steroidogenic genes.
- Orlistat reduced leptin and increased adiponectin levels, correlating with improved fertility markers.
Conclusions:
- Orlistat effectively attenuates obesity-induced impairments in steroidogenesis and spermatogenesis in male rats.
- The drug's beneficial effects are linked to its ability to modulate leptin levels and upregulate steroidogenic pathways.
- Orlistat shows promise as a therapeutic agent to improve fertility potential in overweight and obese men.
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