Effects of obesity and exercise on testicular leptin signal transduction and testosterone biosynthesis in male mice

Abstract

To explore the role of the testicular leptin and JAK-STAT[leptin (LEP)-JAK-STAT] pathway in testosterone biosynthesis during juvenile stages and exercise for weight loss, male C57BL/6J mice were randomly divided into normal-diet and high-fat diet groups. After 10 wk, mice in the high-fat diet-fed group were further divided randomly into obese control, obese moderate-volume exercise, and obese high-volume exercise groups. Mice in the obese moderate-volume exercise group were provided with 2 h/day, 6 days/wk swimming exercise for 8 wk, and mice in the obese high-volume exercise group underwent twice the amount of daily exercise intervention as the obese moderate-volume exercise group. The results showed that a high-fat diet causes obesity, leptin resistance, inhibition of the testicular LEP-JAK-STAT pathway, decreased mRNA and protein expression of steroidogenic factor-1, steroidogenic acute regulatory protein, and the -450 side-chain cleavage enzyme, a decrease in the serum testosterone-to-estradiol ratio, and declines in sperm quality parameters. Both moderate and high-volume exercise were able to reduce body fat and increase the mRNA and protein expression of LEP-JAK-STAT, but only moderate exercise significantly increased the mRNA and protein expression of steroidogenic factor-1, steroidogenic acute regulatory protein, and-450 side-chain cleavage enzyme and significantly reversed the serum testosterone-to-estradiol ratio and sperm quality parameters. These findings suggest that by impairing the testicular LEP-JAK-STAT pathway, early-stage obesity inhibits the biosynthesis of testosterone and sexual development and reduces male reproductive potential. Long-term moderate and high-volume exercise can effectively reduce body fat and improve obesity-induced abnormalities in testicular leptin signal transduction, whereas only moderate-volume exercise can reverse the negative impacts of obesity on male reproductive function.

HC diet inhibited testosterone synthesis by activating endoplasmic reticulum stress in testicular Leydig cells

“…However, there is great interindividual variability in testosterone levels, with the global prevalence of TD varying from 7% to 49% in ageing men. [18][19][20] These studies suggested that impaired testosterone synthesis might be an important mechanism in the process of diet affecting testosterone levels. 4,6 Cholesterol is an essential component of the human diet and performs an important role as a raw material in the synthesis of steroid hormones and vitamin D. 7 A substantial amount of evidence indicates that hypercholesterolaemia is a crucial risk factor for mortality and morbidity, not only for cardiovascular disease 8,9 but also for non-alcoholic fatty liver disease, 10 cancer 11 and Alzheimer's disease 12,13 Our previous epidemiological study demonstrated that low testosterone was related to elevated total cholesterol (TC) in serum from 4114 middle-aged and older Chinese participants, 14 which was consistent with previous research.…”

“…Several studies reported that high-fat diets or high-calorie diets could regulate Leydig cell steroidogenesis by several mechanisms, including dysregulation of the hypothalamic-pituitary-gonadal axis, increases in the leptin signal transduction pathway and inflammatory cytokine release in the testis. [18][19][20] These studies suggested that impaired testosterone synthesis might be an important mechanism in the process of diet affecting testosterone levels. Hence, in this study, we aimed to investigate adverse effects and mechanisms on Leydig cell steroidogenesis in mice fed a HC diet.…”

Cyclophilin D participates in the inhibitory effect of high‐fat diet on the expression of steroidogenic acute regulatory protein

“…A previous study reported that both pharmacological inhibition of ATP synthesis and dissipation of mitochondrial membrane potential (Δψm) could inhibit steroidogenesis owing to the reduced expression of StAR, proving that the StAR activity requires mitochondrial homeostasis. It is reported that HFD could down‐regulate StAR expression in mice . However, whether mitochondrial dyshomeostasis is involved in HFD‐induced StAR expression down‐regulation is still unclear.…”

“…It is reported that HFD could down-regulate StAR expression in mice. 18 However, whether mitochondrial dyshomeostasis is involved in HFD-induced StAR expression down-regulation is still unclear.…”

Protective Role of Eurycoma longifolia Jack Root Extract Against High-Fat Diet Induced Testicular Damage in Sprague-Dawley Rats

“…Recently, many studies have used high-fat diet (HFD) to induce obesity by a nutritional involvement in several experimental animals, HFD has been shown to induce hyperglycemia and whole-body insulin resistance, many investigators have demonstrated that HFD induces lipid metabolic disorder and leads to a lack of male reproductive function, such as decreased serum testosterone level, sexual hormones metabolic disorder, apoptosis of seminiferous tubules cell and a significant deterioration of sperm function parameters, including a decrease in semen volume reduced score for sperm count, decreased motility associated with a significant increase in sperm cell malformation, and disturbing of blood testeis barier integrity. [5][6][7] Recent studies using many herbal medicines exert protective and therapeutic effects on the testes and spermatogenesis in animals fed HFD. Curcumin has been shown to reduce HFD-induced spermatogenesis impairment and apoptosis of the seminiferous tubules.…”