Browsing by Author "Mayank Choubey"

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Adiponectin and Chemerin: Contrary Adipokines in Regulating Reproduction and Metabolic Disorders
(SAGE Publications Inc., 2018) Anusha Singh; Mayank Choubey; Puran Bora; Amitabh Krishna
Metabolic disorders such as obesity and type 2 diabetes are one of the most familiar risk factors in the present time among every age-group. It is associated with altered levels of adipokines such as adiponectin, chemerin, leptin, resistin, visfatin, and so on. Adiponectin is one of the adipocyte-specific protein with novel applications pertaining to metabolism by promoting insulin sensitivity and regulating glucose and fatty acid catabolism, while chemerin is considered as an inhibitor of insulin signaling and glucose catabolism. Other than these established functions, both the adipokines are intimately involved in coordinating reproductive activities, but they exhibit contrary functions. This review is an amalgamation of recent information related to adiponectin and chemerin in male and female reproduction and further its association with metabolism-related reproductive disorders. The direct effect of adiponectin and chemerin on various reproductive parameters has been investigated, but there was a rampant failure to account for in vivo data which gives a broad outlook on the regulatory mechanism of both adiponectin and chemerin related to male and female reproductive functions. Adiponectin is known to promote gonadal activities, while chemerin exerts antigonadal actions. Recent research suggests that high chemerin/low adiponectin ratio plays a vital role in causing dyslipidemia and metabolic syndrome in patients. The dysregulated ratio of adiponectin to chemerin during various metabolic disorders makes it really worthy in relation to an application for therapeutics. Still, a lot regarding both the adipokines has to be explored and brought forward in order to deal with therapeutics of metabolism-related reproductive disorders. © The Author(s) 2018.
Adiponectin/AdipoRs signaling as a key player in testicular aging and associated metabolic disorders
(Academic Press Inc., 2021) Mayank Choubey; Ashutosh Ranjan; Amitabh Krishna
Aging undergoes serious worsening of peripheral organs and vital physiological processes including reproductive performances. Altered white adipose tissue and adipocyte functioning during aging results in ectopic lipid storage/obesity or metabolic derangements, leading to insulin resistance state. Eventually, accelerating cellular senescence thereby enhancing the high risk of age-associated metabolic alterations. Such alterations may cause derangement of numerous physiologically active obesity hormones, known as “adipokines.” Specifically, adiponectin exhibits insulin sensitizing action causing anti-aging and anti-obesity effects via activation of adiponectin receptors (AdipoRs). The male reproductive physiology from reproductive mature stage to advanced senescent stage undergoes insidious detrimental changes. The mechanisms by which testicular functions decline with aging remain largely speculative. Adiponectin has also recently been shown to regulate metabolism and longevity signaling thus prolonging lifespan. Therefore, the strategy for activating adiponectin/AdipoRs signaling pathways are expected to provide a solid basis for the prevention and treatment of aging and obesity-associated reproductive dysfunctions, as well as for ensuring healthy reproductive longevity in humans. © 2021 Elsevier Inc.
Direct actions of adiponectin on changes in reproductive, metabolic, and anti-oxidative enzymes status in the testis of adult mice
(Academic Press Inc., 2019) Mayank Choubey; Ashutosh Ranjan; Puran S. Bora; Fátima Baltazar; Amitabh Krishna
Obesity is a major health problem that is linked to decreased sperm count. It is hypothesized that an obesity-associated reduction in adiponectin secretion may be responsible for impairment of spermatogenesis. Therefore, the aim of the study was to evaluate the direct role of adiponectin in spermatogenesis and steroid synthesis in adult mice. This study showed that adiponectin receptors (AdipoR1 and AdipoR2)were localized in Leydig cells and seminiferous tubules in the testis of adult mice. The result of the in vitro study showed the direct action of adiponectin on spermatogenesis by stimulating cell proliferation (PCNA)and survival (Bcl2)and by suppressing cell apoptosis. Treatment of testis with adiponectin also enhanced transport of the energetic substrates glucose and lactate to protect cells from undergoing apoptosis. Adiponectin treatment further showed a significant reduction in oxidative stress and nitric oxide. Our findings suggest that adiponectin effectively facilitates cell survival and proliferation, as well as protects from apoptosis. Thus, adiponectin treatment may be responsible for enhancing sperm counts. Interestingly, this study showed the stimulatory effect of adiponectin in spermatogenesis but showed an inhibitory effect on testosterone and estradiol synthesis in the testes. Based on the present study, it is hypothesized that systemic adiponectin treatment may be a promising therapeutic strategy for the improvement of spermatogenesis and sperm count. © 2018 Elsevier Inc.
Direct effects of neuropeptide nesfatin-1 on testicular spermatogenesis and steroidogenesis of the adult mice
(Academic Press Inc., 2019) Ashutosh Ranjan; Mayank Choubey; Toshihiko Yada; Amitabh Krishna
Recent studies have revealed nesfatin-1 as a hypothalamic neuropeptide, regulating food intake, energy expenditure and reproduction primarily by acting on the hypothalamic-pituitary-gonadal axis. Nesfatin-1 is also localized in several peripheral tissues including testes. However, functional significance of nesfatin-1 in testicular activities is not yet well documented in mammals. Therefore, this study was aimed to elucidate the direct effects of nesfatin-1 on testicular markers for steroid productions, spermatogenesis, metabolic changes and oxidative stress. The results revealed the expression of both protein and mRNA of nesfatin-1 in the testes of adult mice. The testes treated in vitro with nesfatin-1 showed significant increase in testosterone production, which correlated significantly with increased expression of steroidogenic markers and insulin receptor proteins in the testes. Furthermore, the in vitro treatment with nesfatin-1 showed stimulatory effects on spermatogenesis by promoting cell proliferation (PCNA) and survival (Bcl2), while inhibiting apoptosis (caspase-3) in the testes. The nesfatin-1 treatment in vitro further increased the expression of insulin receptor and GLUT8 proteins, in parallel with increase in the intra-testicular transport of glucose and production of lactate. This nesfatin-1 induced enhanced transport of energy substrate (glucose and lactate) may be responsible for promoting spermatogenesis and steroidogenesis. Nesfatin-1 significantly reduced oxidative stress and nitric oxide, which may also be responsible for stimulatory effects on testicular activities. The present finding suggests that nesfatin-1 acts via paracrine manner to increase sperm count and fertility, thus promoting the testicular function. © 2018 Elsevier Inc.
Hepatoprotective role of Pueraria tuberosa water extract (PTWE) in CCl4-induced liver injury through different signaling pathways
(Springer, 2024) Prerana Aditi; Vahab Ali; Mayank Choubey; Munichandra Babu Tirumalasetty; Harsh Pandey; Shivani Srivastava; Yamini Bhusan Tripathi
Liver damage is one of the leading diseases, resulting in high morbidity. It is more relevant in the context of bad food habits, environmental pollution, and biohazards. The present study aimed to investigate the role of semi-purified water extract of Pueraria tuberosa on carbon tetrachloride (CCl4)-induced liver injury and also its mechanism of action regarding transcriptomic status in liver tissue about inflammation, hypoxia, and apoptosis. Liver injury was induced in Charles foster rats via intraperitoneal injection (IP) of CCl4, 0.1 mg/100gm body weight, diluted with olive oil (30%) twice a week for 20 days. PTWE was given via oral route daily simultaneously with CCl4 at the dose of 50 mg/100 g and 100 mg/100 g body weight. On 21st day all rats were sacrificed. Biochemical tests and histological studies were done. mRNA expression of bcl-2, caspase-3, bax, and GAPDH and protein expression of iNOS, BCL-2, HIF-1α, VEGF, β-Tubulin was done. Simultaneous treatment of PTWE with CCl4 decreased the level of NO, PC, SGOT, SGPT, ALP, LPO, and iNOS, HIF-1α, VEGF, bax, and caspase-3 expression. In addition, PTWE increased the SOD, Catalase, GSH level, and bcl-2 expression as well as normalized the architecture of hepatic tissue. Immunohistochemical staining showed the decreased accumulation of CD45, VEGF, α-SMA, collagen, and desmin after PTWE treatment. This study suggests that PTWE inhibits fibrosis by reducing the accumulation of α-SMA, collagen, and desmin in CCl4-induced toxicity. The mechanism of protective action is through its anti-inflammatory (iNOS, NO, CD45), anti-apoptotic (bcl-2, bax, caspase-3), anti-hypoxic (HIF-1α, VEGF), and anti-fibrotic (α-SMA, collagen, desmin) potentials. © The Author(s), under exclusive licence to Institute of Korean Medicine, Kyung Hee University 2024.
Hepatoprotective role of Pueraria tuberosa water extract (PTWE) in CCl4-induced liver injury through different signaling pathways
(Springer, 2025) Prerana Aditi; Vahab Ali; Mayank Choubey; Munichandra Babu Tirumalasetty; Harsh Pandey; Shivani Srivastava; Yamini Bhusan Tripathi
Liver damage is one of the leading diseases, resulting in high morbidity. It is more relevant in the context of bad food habits, environmental pollution, and biohazards. The present study aimed to investigate the role of semi-purified water extract of Pueraria tuberosa on carbon tetrachloride (CCl4)-induced liver injury and also its mechanism of action regarding transcriptomic status in liver tissue about inflammation, hypoxia, and apoptosis. Liver injury was induced in Charles foster rats via intraperitoneal injection (IP) of CCl4, 0.1 mg/100gm body weight, diluted with olive oil (30%) twice a week for 20 days. PTWE was given via oral route daily simultaneously with CCl4 at the dose of 50 mg/100 g and 100 mg/100 g body weight. On 21st day all rats were sacrificed. Biochemical tests and histological studies were done. mRNA expression of bcl-2, caspase-3, bax, and GAPDH and protein expression of iNOS, BCL-2, HIF-1α, VEGF, β-Tubulin was done. Simultaneous treatment of PTWE with CCl4 decreased the level of NO, PC, SGOT, SGPT, ALP, LPO, and iNOS, HIF-1α, VEGF, bax, and caspase-3 expression. In addition, PTWE increased the SOD, Catalase, GSH level, and bcl-2 expression as well as normalized the architecture of hepatic tissue. Immunohistochemical staining showed the decreased accumulation of CD45, VEGF, α-SMA, collagen, and desmin after PTWE treatment. This study suggests that PTWE inhibits fibrosis by reducing the accumulation of α-SMA, collagen, and desmin in CCl4-induced toxicity. The mechanism of protective action is through its anti-inflammatory (iNOS, NO, CD45), anti-apoptotic (bcl-2, bax, caspase-3), anti-hypoxic (HIF-1α, VEGF), and anti-fibrotic (α-SMA, collagen, desmin) potentials. © The Author(s), under exclusive licence to Institute of Korean Medicine, Kyung Hee University 2024.
Immunohistochemical localization and possible functions of nesfatin-1 in the testis of mice during pubertal development and sexual maturation
(Springer Netherlands, 2019) Ashutosh Ranjan; Mayank Choubey; Toshihiko Yada; Amitabh Krishna
The study was aimed to address the role of nesfatin-1 on the sexual maturation of testis during the pubertal transition. The immunostaining of testis suggested nesfatin-1 is expressed in Leydig cells with pubertal maturation. The pre-pubertal mice for in vivo study were randomly divided in three groups; (a) control-saline (b) treated with low (0.25 nM) dose of nesfatin-1/gbw/day and (c) treated with high (1.25 nM) dose nesfatin-1/gbw/day. Histological analysis showed that nesfatin-1 loaded mice showed facilitated maturation of testis. Western blot analysis on various protein expressions upon injection of nesfatin-1 into pre-pubertal mice suggested that expressions of proteins involving steroid hormone production, spermatogenic markers (PCNA, Bcl2, AR), glucose uptake-related proteins (GLUT8 and insulin receptor) and GnRH-R and GPR-54 proteins were facilitated. Both of lactose dehydrogenase activity and lactate levels were increased. The treatment with nesfatin-1 also reduced oxidative stress, which further facilitates testicular functions during puberty. The treatment of nesfatin-1 on cultured testis also supports in vivo findings as evident by the increased testosterone production and StAR protein expression as well as increased glucose and lactate production. In sum, our data report for the first time the accelerative role of nesfatin-1 on spermatogenesis and steroidogenesis of pre-pubertal male mice by directly acting on the testis coupled with the advancement of puberty. © 2019, Springer Nature B.V.
Protective role of adiponectin against testicular impairment in high-fat diet/streptozotocin-induced type 2 diabetic mice
(Elsevier B.V., 2020) Mayank Choubey; Ashutosh Ranjan; Puran S. Bora; Amitabh Krishna
Type 2 diabetes (T2D) is the most common endocrine and metabolic disorder, leading to reproductive impairments and infertility in male. Our recent study showed crucial role of adiponectin in the regulation of testicular functions, and the circulating level of adiponectin declines in diabetes. The current study thus aimed to examine the efficacy of adiponectin in improving testicular dysfunction in high-fat diet/streptozotocin-induced T2D mice. T2D was induced in pre-pubertal mice fed with high-fat diet for ∼10 weeks followed by a single dose of streptozotocin. T2D mice showed presence of increased body mass, hyperglycemia, hyperinsulinemia, insulin resistance, increased oxidative stress, and declined serum testosterone compared to vehicle-treated control mice. The spermatogenic, steroidogenic, metabolic, and antioxidative parameters were evaluated in T2D mice treated with adiponectin for both two and four weeks. The exogenous administration of adiponectin to T2D mice showed enhanced serum testosterone and expression of testicular steroidogenic markers proteins, insulin receptor and GLUT8 proteins, increase in intra-testicular concentrations of glucose and lactate and activity of LDH and antioxidant enzymes compared to the levels in untreated T2D mice. This suggests that treatment of adiponectin effectively improves testicular functions by increasing expression of insulin receptor-mediated increased transport of energy substrate (glucose and lactate) and a marked reduction in oxidative stress are the possible mechanism by which adiponectin effectively improves testicular function in T2D mice. © 2019 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM)
Role of adiponectin as a modulator of testicular function during aging in mice
(Elsevier B.V., 2019) Mayank Choubey; Ashutosh Ranjan; Puran S. Bora; Fatima Baltazar; Luc J. Martin; Amitabh Krishna
The mechanisms by which testicular functions decline with aging remain largely speculative. Our recent finding showed the importance of adiponectin in the regulation of testicular functions, whereas its concentration declines during male infertility. Thus, the aim of present study was to explore the potential role of adiponectin during aging. The changes in adiponectin, adiponectin-receptors, and insulin receptor proteins expression in the testis were evaluated and compared with the testicular parameters, mass, and testosterone level in the mice from early post-natal to late senescence period. Further, the current study has examined the effect of exogenous adiponectin treatment on testicular functions in aged mice. The results showed a significant decline in adiponectin/adiponectin-receptors expression simultaneously with a significant decline in testicular mass, insulin receptor expression and testosterone synthesis in the testis of aged mice. Exogenous treatment of adiponectin to aged mice resulted in marked improvements in testicular mass, histological features (cells proliferation), insulin receptor expression, testicular glucose uptake, anti-oxidative enzymes activity and testosterone synthesis as compared with the control. Based on these findings, it may be concluded that a marked decline in adiponectin synthesis and action results in decreased insulin sensitivity (development of insulin resistance) and increased oxidative stress which consequently suppresses testicular functions during aging. This study further showed that treatment with adiponectin ameliorates reduced testicular functions by enhanced expression of insulin receptor in the testis of senescent mice. It is thus hypothesized that systemic adiponectin treatment could be a promising therapeutic strategy for improvement of testosterone production and sperm counts during aging. © 2018 Elsevier B.V.