Leptin and inflammatory factors play a synergistic role in the regulation of reproduction in male mice through hypothalamic kisspeptin-mediated energy balance

Abstract Background Energy 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. He...

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Main Authors: Bo Chang, Chenglin Song, Haining Gao, Tie Ma, Tao Li, Qianhe Ma, Tingting Yao, Meng Wang, Jing Li, Xuejie Yi, Donghui Tang, Shicheng Cao
Format: Article
Language:English
Published: BMC 2021-01-01
Series:Reproductive Biology and Endocrinology
Subjects:
Online Access:https://doi.org/10.1186/s12958-021-00698-0
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spelling doaj-2506b63d4ad24497987ab0de6f6df4b32021-01-24T12:10:00ZengBMCReproductive Biology and Endocrinology1477-78272021-01-0119111310.1186/s12958-021-00698-0Leptin and inflammatory factors play a synergistic role in the regulation of reproduction in male mice through hypothalamic kisspeptin-mediated energy balanceBo Chang0Chenglin Song1Haining Gao2Tie Ma3Tao Li4Qianhe Ma5Tingting Yao6Meng Wang7Jing Li8Xuejie Yi9Donghui Tang10Shicheng Cao11Exercise and Health Research Center/Department of Kinesiology, Shenyang Sport UniversityExercise and Health Research Center/Department of Kinesiology, Shenyang Sport UniversityExercise and Health Research Center/Department of Kinesiology, Shenyang Sport UniversityExercise and Health Research Center/Department of Kinesiology, Shenyang Sport UniversityExercise and Health Research Center/Department of Kinesiology, Shenyang Sport UniversityExercise and Health Research Center/Department of Kinesiology, Shenyang Sport UniversityExercise and Health Research Center/Department of Kinesiology, Shenyang Sport UniversityExercise and Health Research Center/Department of Kinesiology, Shenyang Sport UniversityExercise and Health Research Center/Department of Kinesiology, Shenyang Sport UniversityExercise and Health Research Center/Department of Kinesiology, Shenyang Sport UniversityPE College of Beijing Normal UniversityDepartment of Sports Medicine, School of Public and Basic Sciences, China Medical UniversityAbstract Background Energy 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. Methods Four-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. Results Compared 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. Conclusion During changes in energy balance, leptin and inflammation jointly regulate kisspeptin expression on the HPT axis.https://doi.org/10.1186/s12958-021-00698-0Energy balanceInflammationLeptinKisspeptinHypogonadotropic hypogonadism
collection DOAJ
language English
format Article
sources DOAJ
author Bo Chang
Chenglin Song
Haining Gao
Tie Ma
Tao Li
Qianhe Ma
Tingting Yao
Meng Wang
Jing Li
Xuejie Yi
Donghui Tang
Shicheng Cao
spellingShingle Bo Chang
Chenglin Song
Haining Gao
Tie Ma
Tao Li
Qianhe Ma
Tingting Yao
Meng Wang
Jing Li
Xuejie Yi
Donghui Tang
Shicheng Cao
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
Energy balance
Inflammation
Leptin
Kisspeptin
Hypogonadotropic hypogonadism
author_facet Bo Chang
Chenglin Song
Haining Gao
Tie Ma
Tao Li
Qianhe Ma
Tingting Yao
Meng Wang
Jing Li
Xuejie Yi
Donghui Tang
Shicheng Cao
author_sort Bo Chang
title Leptin and inflammatory factors play a synergistic role in the regulation of reproduction in male mice through hypothalamic kisspeptin-mediated energy balance
title_short Leptin and inflammatory factors play a synergistic role in the regulation of reproduction in male mice through hypothalamic kisspeptin-mediated energy balance
title_full Leptin and inflammatory factors play a synergistic role in the regulation of reproduction in male mice through hypothalamic kisspeptin-mediated energy balance
title_fullStr Leptin and inflammatory factors play a synergistic role in the regulation of reproduction in male mice through hypothalamic kisspeptin-mediated energy balance
title_full_unstemmed Leptin and inflammatory factors play a synergistic role in the regulation of reproduction in male mice through hypothalamic kisspeptin-mediated energy balance
title_sort leptin and inflammatory factors play a synergistic role in the regulation of reproduction in male mice through hypothalamic kisspeptin-mediated energy balance
publisher BMC
series Reproductive Biology and Endocrinology
issn 1477-7827
publishDate 2021-01-01
description Abstract Background Energy 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. Methods Four-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. Results Compared 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. Conclusion During changes in energy balance, leptin and inflammation jointly regulate kisspeptin expression on the HPT axis.
topic Energy balance
Inflammation
Leptin
Kisspeptin
Hypogonadotropic hypogonadism
url https://doi.org/10.1186/s12958-021-00698-0
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