ArticleEndocrine2018
Downregulation of leptin receptor and kisspeptin/GPR54 in the murine hypothalamus contributes to male hypogonadism caused by high-fat diet-induced obesity.
Article in Endocrine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 41 citations in OpenAlex.
- Alternate-day fasting enhances leptin sensitivity via JMJD3-dependent epigenetic regulation of the leptin receptor in the hypothalamus.The Journal of nutritional biochemistry · 2026Article
- Beyond weight loss: Disentangling the direct effects of semaglutide vs equivalent calorie restriction on reproductive systems of male and female rats.Molecular metabolism · 2026Article
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- Beyond satiety: unraveling the complex roles of POMC neurons in behavior and metabolism.Reviews in endocrine & metabolic disorders · 2026Review
- Melatonin attenuates reproductive toxicity of prothioconazole and its metabolite via spermatogenesis and oxidative stress.Communications biology · 2026Article
- Kisspeptin as a test of hypothalamic dysfunction in pubertal and reproductive disorders.Andrology · 2026Review
- Testosterone and Obesity in an Aging Society.Biomolecules · 2025Review
- Sex Hormone-Binding Globulin and Metabolic Syndrome in Children and Adolescents: A Focus on Puberty.Metabolites · 2025Review
- Obesity Epidemic and Its Impact on Female Fertility: Current Understanding and Future Directions.Cureus · 2025Review
- Maternal high-fat or low-protein diets promote autism-related behavior and altered social behavior within groups in offspring male mice.Scientific reports · 2024Article
- Differential Impairment Mechanism of Sperm Production via Induction of miR-34c-Activated Apoptosis and Spermatogenesis Pathway in Diet-Induced Obesity and Resistant Mice and GC-1 Spg Cells.International journal of molecular sciences · 2024Article
- Neuroendocrine disturbances in women with functional hypothalamic amenorrhea: an update and future directions.Endocrine · 2024Review
- Article
- LepRb+ cell-specific deletion of Slug mitigates obesity and nonalcoholic fatty liver disease in mice.The Journal of clinical investigation · 2023Article
- Obesity, type 2 diabetes, and testosterone in ageing men.Reviews in endocrine & metabolic disorders · 2022Review
- The role of leptin and low testosterone in obesity.International journal of impotence research · 2022Review
- Regulation of Metabolic Health by an "Olfactory-Hypothalamic Axis" and Its Possible Implications for the Development of Therapeutic Approaches for Obesity and T2D.Cellular and molecular neurobiology · 2022Review
- Review
- The Role of Peptide Hormones Discovered in the 21st Century in the Regulation of Adipose Tissue Functions.Genes · 2021Review
- Leptin and inflammatory factors play a synergistic role in the regulation of reproduction in male mice through hypothalamic kisspeptin-mediated energy balance.Reproductive biology and endocrinology : RB&E · 2021Article
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
purposeObesity may lead to male hypogonadism, the underlying mechanism of which remains unclear. In the present study, we established a murine model of male hypogonadism caused by high-fat diet-induced obesity to verify the following hypotheses: 1) an increased leptin level may be related to decreased secretion of GnRH in obese males, and 2) repression of kisspeptin/GPR54 in the hypothalamus, which is associated with increased leptin levels, may account for the decreased secretion of GnRH and be involved in secondary hypogonadism (SH) in obese males.
methodsMale mice were fed high-fat diet for 19 weeks and divided by body weight gain into diet-induced obesity (DIO) and diet-induced obesity resistant (DIO-R) group. The effect of obesity on the reproductive organs in male mice was observed by measuring sperm count and spermatozoid motility, relative to testis and epididymis weight, testosterone levels, and pathologic changes. Leptin, testosterone, estrogen, and LH in serum were detected by ELISA method. Leptin receptor (Ob-R), Kiss1, GPR54, and GnRH mRNA were measured by real-time PCR in the hypothalamus. Expression of kisspeptin and Ob-R protein was determined by Western blotting. Expression of GnRH and GPR54 protein was determined by immunohistochemical analysis.
resultsWe found that diet-induced obesity decreased spermatozoid motility, testis and epididymis relative coefficients, and plasma testosterone and luteinizing hormone levels. An increased number and volume of lipid droplets in Leydig cells were observed in the DIO group compared to the control group. Significantly, higher serum leptin levels were found in the DIO and DIO-R groups. The DIO and DIO-R groups showed significant downregulation of the GnRH, Kiss1, GPR54, and Ob-R genes. We also found decreased levels of GnRH, kisspeptin, GPR54, and Ob-R protein in the DIO and DIO-R groups.
conclusionsThese lines of evidence suggest that downregulation of Ob-R and kisspeptin/GPR54 in the murine hypothalamus may contribute to male hypogonadism caused by high-fat diet-induced obesity.
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