Abstract
BackgroundEnergy balance is closely related to reproductive function, wherein hypothalamic kisspeptin mediates regulation of the energy balance. However, the central mechanism of kisspeptin in the regulation of male reproductive function under different energy balance states is unclear. Here, high-fat diet (HFD) and exercise were used to change the energy balance to explore the role of leptin and inflammation in the regulation of kisspeptin and the hypothalamic-pituitary-testis (HPT) axis.MethodsFour-week-old male C57BL/6 J mice were randomly assigned to a normal control group (n = 16) or an HFD (n = 49) group. After 10 weeks of HFD feeding, obese mice were randomly divided into obesity control (n = 16), obesity moderate-load exercise (n = 16), or obesity high-load exercise (n = 17) groups. The obesity moderate-load exercise and obesity high-load exercise groups performed exercise (swimming) for 120 min/day and 120 min × 2 times/day (6 h interval), 5 days/week for 8 weeks, respectively.ResultsCompared to the mice in the normal group, in obese mice, the mRNA and protein expression of the leptin receptor, kiss, interleukin-10 (IL-10), and gonadotropin-releasing hormone (GnRH) decreased in the hypothalamus; serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone levels and sperm quality decreased; and serum leptin, estradiol, and tumor necrosis factor-α (TNF-α) levels and sperm apoptosis increased. Moderate- and high-load exercise effectively reduced body fat and serum leptin levels but had the opposite effects on the hypothalamus and serum IL-10 and TNF-α levels. Moderate-load exercise had anti-inflammatory effects accompanied by increased mRNA and protein expression of kiss and GnRH in the hypothalamus and increased serum FSH, LH, and testosterone levels and improved sperm quality. High-load exercise also promoted inflammation, with no significant effect on the mRNA and protein expression of kiss and GnRH in the hypothalamus, serum sex hormone level, or sperm quality. Moderate-load exercise improved leptin resistance and inflammation and reduced the inhibition of kisspeptin and the HPT axis in obese mice. The inflammatory response induced by high-load exercise may counteract the positive effect of improving leptin resistance on kisspeptin and HPT.ConclusionDuring changes in energy balance, leptin and inflammation jointly regulate kisspeptin expression on the HPT axis.
Highlights
Energy balance is closely related to reproductive function, wherein hypothalamic kisspeptin mediates regulation of the energy balance
Long-term energy imbalance affects the development and physiological function of the hypothalamic– pituitary–gonadal (HPG) axis in adolescence and adulthood [1, 2]. Both a negative energy balance caused by long-term food restriction [2] and positive energy balance induced by dietary obesity [3] can lead to decreased serum testosterone levels, spermatogenesis, and sexual dysfunction in men, often accompanied by a decrease in serum follicle-stimulating hormone (FSH) and luteinizing hormone (LH)
Five obesity-resistant mice were removed from the high-fat diet (HFD) group, and the obese mice were randomly assigned to three groups: obesity control (OC, n = 16), obesity moderate-volume exercise (OME, n = 16), and obesity heavy-volume exercise (OHE, n = 17)
Summary
Energy balance is closely related to reproductive function, wherein hypothalamic kisspeptin mediates regulation of the energy balance. Long-term energy imbalance affects the development and physiological function of the hypothalamic– pituitary–gonadal (HPG) axis in adolescence and adulthood [1, 2] Both a negative energy balance caused by long-term food restriction [2] and positive energy balance induced by dietary obesity [3] can lead to decreased serum testosterone levels, spermatogenesis, and sexual dysfunction in men, often accompanied by a decrease in serum follicle-stimulating hormone (FSH) and luteinizing hormone (LH). Several studies have confirmed that longterm moderate- or heavy-load exercise can effectively increase energy consumption, cause the body to have a negative energy balance, and reduce body fat. We predicted that high-fat diet (HFD) and exercise-induced changes in the energy balance affect male reproductive function through hypothalamic kisspeptin
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