scholarly journals Orlistat reverses intratesticular lactate transport decline and infertility in male obese rats

Reproduction ◽  
2020 ◽  
Vol 160 (6) ◽  
pp. 863-872 ◽  
Author(s):  
Joseph Bagi Suleiman ◽  
Victor Udo Nna ◽  
Zaida Zakaria ◽  
Zaidatul Akmal Othman ◽  
Ainul Bahiyah Abu Bakar ◽  
...  
Keyword(s):  
Erectile Dysfunction ◽  
Glucose Metabolism ◽  
Sexual Behaviour ◽  
Mating Behaviour ◽  
Male Rats ◽  
Cgmp Level ◽  
Mrna Levels ◽  
Sprague Dawley ◽  
Obese Rats ◽  
Fertility Potential

Obesity and its accompanying complications predispose to abnormal testicular glucose metabolism, penile erectile dysfunction and subfertility. This study examined the potentials of orlistat in attenuating erectile dysfunction and fertility decline in high-fat diet (HFD)-induced obesity in male rats. Eighteen adult male Sprague–Dawley rats whose weights were between 250 and 300 g were divided into three groups (n = 6/group) namely: normal control (NC), HFD and HFD + orlistat (10 mg/kg body weight/day co-administered for 12 weeks) (HFD+O). During the 11th and 12th week, mating behaviour and fertility parameters were evaluated, and parameters of glucose metabolism were assessed at the end of the 12th week. Orlistat increased testicular mRNA levels of glucose transporters (Glut1 and Glut3), monocarboxylate transporters (Mct2 and Mct4) and lactate dehydrogenase type C (Ldhc), decreased intratesticular lactate and glucose levels, and LDH activity in obese rats. Furthermore, orlistat increased superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST) and glutathione reductase (GR) activities, and total antioxidant capacity (TAC), but decreased malondialdehyde level in the penis of obese rats. Similarly, orlistat improved penile cGMP level, sexual behaviour and fertility outcome in obese rats. Penile cGMP level correlated positively with total mounts and intromissions but correlated negatively with mount/intromission ratio. Orlistat improves fertility potential in obese state by targeting testicular lactate metabolism, penile oxidative stress and sexual behaviour in rats. Therefore, orlistat shows a promising protective effect and may preserve the fertility potential of obese men.

scholarly journals Testosterone activates glucose metabolism through AMPK and androgen signaling in cardiomyocyte hypertrophy

2021 ◽  
Vol 54 (1) ◽  
Author(s):  
Mayarling Francisca Troncoso ◽  
Mario Pavez ◽  
Carlos Wilson ◽  
Daniel Lagos ◽  
Javier Duran ◽  
...  
Keyword(s):  
Glucose Metabolism ◽  
Cardiac Hypertrophy ◽  
Glucose Uptake ◽  
Male Rats ◽  
Cardiomyocyte Hypertrophy ◽  
Mrna Levels ◽  
Elevated Glucose ◽  
Amp Activated Protein Kinase ◽  
Cultured Cardiomyocytes

Abstract Background Testosterone regulates nutrient and energy balance to maintain protein synthesis and metabolism in cardiomyocytes, but supraphysiological concentrations induce cardiac hypertrophy. Previously, we determined that testosterone increased glucose uptake—via AMP-activated protein kinase (AMPK)—after acute treatment in cardiomyocytes. However, whether elevated glucose uptake is involved in long-term changes of glucose metabolism or is required during cardiomyocyte growth remained unknown. In this study, we hypothesized that glucose uptake and glycolysis increase in testosterone-treated cardiomyocytes through AMPK and androgen receptor (AR). Methods Cultured cardiomyocytes were stimulated with 100 nM testosterone for 24 h, and hypertrophy was verified by increased cell size and mRNA levels of β-myosin heavy chain (β-mhc). Glucose uptake was assessed by 2-NBDG. Glycolysis and glycolytic capacity were determined by measuring extracellular acidification rate (ECAR). Results Testosterone induced cardiomyocyte hypertrophy that was accompanied by increased glucose uptake, glycolysis enhancement and upregulated mRNA expression of hexokinase 2. In addition, testosterone increased AMPK phosphorylation (Thr172), while inhibition of both AMPK and AR blocked glycolysis and cardiomyocyte hypertrophy induced by testosterone. Moreover, testosterone supplementation in adult male rats by 5 weeks induced cardiac hypertrophy and upregulated β-mhc, Hk2 and Pfk2 mRNA levels. Conclusion These results indicate that testosterone stimulates glucose metabolism by activation of AMPK and AR signaling which are critical to induce cardiomyocyte hypertrophy.

scholarly journals Aphrodisiac Activity of Eulophia macrobulbon Extract on Erectile Dysfunction in Male Aged Rats

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Watcharaporn Preedapirom ◽  
Kanokwan Changwichit ◽  
Piyarat Srisawang ◽  
Kornkanok Ingkaninan ◽  
Pornnarin Taepavarapruk
Keyword(s):  
Erectile Dysfunction ◽  
Serum Testosterone ◽  
Cyclic Guanosine Monophosphate ◽  
Guanosine Monophosphate ◽  
Sildenafil Citrate ◽  
Male Rats ◽  
Cgmp Level ◽  
Seminiferous Tubules ◽  
Aged Rats ◽  
Sexual Performance

This study investigated the effect of Eulophia macrobulbon (EM) extract on sexual performance in aged-related erectile dysfunction (ED) rats. The ethanol EM extract at the doses of 15, 150, and 450 and sildenafil citrate at the dose of 5 mg/kg body weight (BW) were administered orally to the aged male rats once daily for 21 days. Mating parameters and intracavernosal pressure (ICP) were measured to evaluate their sexual and erection functions. Numbers of sperm and sperm motility as well as the diameter of seminiferous tubules were observed. The serum testosterone and 3’,5’-cyclic guanosine monophosphate (cGMP) concentration in the rat penile tissue were analyzed. The results showed the significant increased sexual motivation, copulatory performance, and ICP of aged rats treated with sildenafil citrate and all doses of EM extract as compared to control aged rats. Moreover, their serum testosterone levels were slightly increased and significant increase in penile cGMP concentration was observed in these aged rats treated with sildenafil citrate and EM extract. The results suggest that treatment with EM could inhibit activity of PDE5 in penile tissue resulting in the increased cGMP level and bring to the improvement of erectile function and sexual performance.

Weight reduction increases adipose but decreases cardiac LPL in reduced-obese Zucker rats

1991 ◽  
Vol 261 (2) ◽  
pp. E246-E251 ◽  
Author(s):  
D. H. Bessesen ◽  
A. D. Robertson ◽  
R. H. Eckel
Keyword(s):  
Adipose Tissue ◽  
Cardiac Muscle ◽  
Weight Reduction ◽  
Zucker Rats ◽  
Mrna Levels ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Obese Rats ◽  
Obese Zucker Rats ◽  
Coordinate Changes

Lipoprotein lipase (LPL) activity and mRNA levels were measured in cardiac muscle and adipose tissue from lean, obese, and weight-stable reduced-obese Zucker rats, both fasted and 2 h after feeding. Fasting epididymal fat LPL activity was substantially higher in obese rats relative to lean rats [6.9 vs. 0.2 nmol free fatty acid (FFA).10(6) cells-1.min-1; P = 0.0001], and was higher still in reduced-obese rats (15.7 nmol FFA.10(6) cells-1.min-1; P = 0.002). Adipose tissue LPL increased with feeding in all three groups. In marked contrast, fasting cardiac muscle LPL was lower in obese rats relative to lean (28.8 vs. 38.5 nmol FFA.g-1.min-1; P = 0.0064) and was lower still in reduced-obese rats (14.5 nmol FFA.g-1.min-1; P = 0.0001). LPL mRNA levels increased in adipose tissue along with enzyme activity; however, the magnitude of the changes were relatively small, suggesting that the primary regulatory steps are posttranslational. Weight reduction studies were also carried out in Sprague-Dawley rats with similar results. These studies show that sustained weight reduction results in coordinate changes in tissue-specific LPL, favoring delivery of lipoprotein triglyceride fatty acids to adipose tissue relative to cardiac muscle and the restoration of energy stores.

scholarly journals Endocrine, metabolic and cardioprotective effects of hexarelin in obese Zucker rats

2000 ◽  
Vol 166 (3) ◽  
pp. 529-536 ◽  
Author(s):  
V De Gennaro-Colonna ◽  
G Rossoni ◽  
D Cocchi ◽  
AE Rigamonti ◽  
F Berti ◽  
...  
Keyword(s):  
Chronic Treatment ◽  
Plasma Cholesterol ◽  
Left Ventricular ◽  
Male Rats ◽  
Zucker Rats ◽  
Coronary Perfusion ◽  
Mrna Levels ◽  
Obese Rats ◽  
Obese Zucker Rats ◽  
Plasma Gh

Genetically obese male Zucker rats have an impaired secretion of GH, coupled to hyperinsulinemia, hyperlipidemia and glucose intolerance. The aim of this study was to evaluate whether a chronic treatment with hexarelin, a synthetic enkephalin-derived hexapeptide with a potent GH-releasing activity, might be able to ameliorate the somatotropic function and reverse some metabolic alterations associated with obesity in male obese Zucker rats. Furthermore, as decreased GH secretion and insulin resistance are associated with increased cardiovascular risk, we also tested the capacity of hexarelin to prevent postischemic ventricular dysfunction in hearts of male obese Zucker rats. Obese and lean male rats of the Zucker strain were treated with hexarelin (80 microgram/kg, b.i.d., s.c.) or saline (1 ml/kg, b.i.d., s.c.) for 30 days. An acute hexarelin injection (80 microgram, s.c.) at the 28th day of treatment elicited a rise in plasma GH levels in ! lean but not in obese rats (pretreated or not with hexarelin); lean rats chronically treated with hexarelin showed a greater increase in plasma GH as compared with control counterparts. At the end of the experiment, pituitary GH mRNA levels were significantly reduced in obese rats and hexarelin administration failed to increase pituitary GH mRNA and IGF-I concentrations in plasma and heart. Chronic treatment with hexarelin increased insulinemia and blood glucose levels in obese but not in lean rats, left unaltered the high triglyceride levels but significantly decreased plasma cholesterol concentrations in obese rats. Heart preparations from lean and obese Zucker rats treated with saline, subjected to low flow ischemia and reperfusion, showed at reperfusion: a) a low recovery of postischemic left ventricular developed pressure (LVDP), coupled to a substantial increase in coronary perfusion pressure, and b) a marked increase in creatine kinase released in the perfusates. Hexare! lin administration for 30 days counteracted the heart ischemic damage both in lean and obese Zucker rats. In fact, the recovery of LVDP at reperfusion was significantly higher than in controls and the increase in coronary resistance was minimal. Collectively, these data indicate that a 30-day treatment with hexarelin was unable to improve somatotropic function in male obese Zucker rats but was successful in decreasing plasma cholesterol concentrations. Hexarelin exerted a cardioprotective effect in both lean and obese rats. The heart-protective activity afforded by the peptide was divorced from any stimulation of the GH axis and is probably exerted through activation of specific cardiac receptors.

Sexual Activity and Urinary Steroids in Man with special reference to Male Homosexuality

1969 ◽  
Vol 115 (529) ◽  
pp. 1413-1415 ◽  
Author(s):  
Kenneth Dewhurst
Keyword(s):  
Sexual Behaviour ◽  
Mating Behaviour ◽  
Gonadal Hormones ◽  
Male Rats ◽  
Male Homosexuality ◽  
Dual Effect ◽  
Urinary Steroids ◽  
The Central Nervous System ◽  
Excitatory Action ◽  
Activity Cycles

In his Upjohn lecture Professor G. W. Harris (1964) reviewed experiments on the effects of gonadal hormones on the sexual behaviour of animals. He compared sexual behaviour patterns of male rats castrated on the first day of life with those of adult castrates. When fully grown, these day-old castrates were either primed with oestrogen and progesterone and tested for female mating behaviour, or they were given testosterone and tested for male behaviour with receptive females. Thus, Harris was able to demonstrate bisexual behaviour (mediated through hypothalamic-pituitary pathways) with female type activity cycles occurring in male rats. These experiments suggest that gonadal hormones exert a dual effect. During the early phase of development they act inductively, and later in the adult they exert an excitatory action on the central nervous system.

Failure of the synthetic androgen 17β-hydroxy-17α-methylestra-4,9,11-triene-3-one (methyltrienolone, R1881) to duplicate the activational effect of testosterone on mating in castrated male rats

1987 ◽  
Vol 113 (1) ◽  
pp. 15-20 ◽  
Author(s):  
M. J. Baum ◽  
P. A. Kingsbury ◽  
M. S. Erskine
Keyword(s):  
Androgen Receptor ◽  
Propylene Glycol ◽  
Sexual Behaviour ◽  
Receptor Agonist ◽  
Androgen Receptors ◽  
Mating Behaviour ◽  
Male Rats ◽  
Intact Male ◽  
Low Level

ABSTRACT Administration of the synthetic steroid, 17β-hydroxy-17α-methyl-estra-4,9,11-triene-3-one (methyltrienolone, R1881), which is an androgen receptor agonist not metabolized in vivo, at doses of 400, 800 or 2400 μg/kg s.c. in propylene glycol stimulated mounting and ejaculation only slightly in sexually experienced castrated rats. A similar low level of mating was observed in a group of castrated rats given testosterone at doses of 400 followed by 800 μg/kg. However, when treated with a higher dose of testosterone (2400 μg/kg) these castrated rats displayed significantly higher levels of mounting and ejaculation than rats treated with any of the doses of R1881. Also, when this higher dosage of testosterone was substituted for each dose of R1881, significant increments in mounting and ejaculation occurred in all groups. These findings show that R1881 is only marginally effective in restoring sexual behaviour in castrated rats, suggesting that the activation of neural androgen receptors cannot by itself account for the activational effect of testosterone on mating behaviour in gonadally intact male rats. J. Endocr. (1987) 113,15–20

scholarly journals Methanolic Extract of Maytenus Procumbens Roots Ameliorates Erectile Dysfunction in Fructose-Streptozotocin Induced Type 2 Diabetic in Rats

2021 ◽  
Author(s):  
Nkosinathi Cele ◽  
Sihle Ephraim Mabhida ◽  
Thembeka Nyawo ◽  
Khanyisani Ziqubu ◽  
Sthandiwe Mazibuko-Mbeje ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Erectile Dysfunction ◽  
Methanolic Extract ◽  
Inhibitory Effect ◽  
Diabetic Rats ◽  
Male Rats ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
High Fructose

Erectile dysfunction (ED) due to diabetes mellitus remains difficult to treat despite advances in pharmacotherapeutic approaches in the field. Therefore, this study investigated the erectogenic effect of the methanolic extract of Maytenus procumbens roots on type 2 diabetes in rats. The fructose-streptozotocin model was used to induce type 2 diabetes-linked ED in male rats. The sexually active male Sprague Dawley rats were randomly divided into two major groups; normal group and high fructose fed group for 120 days. After 120 days, the high fructose fed group rats were given a single intraperitoneal injection of a freshly prepared streptozotocin solution (30 mg/kg). The diabetic ED rats were orally administered with the extract at 250 mg/kg, daily for 28 days. The serum, brain and penile tissues were removed for biochemical analysis and protein expression. Increased testosterone level, mounting frequency, reduced blood glucose level and serum fructosamine content was observed after 28 days of treatment in diabetic rats. Methanolic extract also exhibited an inhibitory effect on arginase, AChE, and ACE activities. The crude extract further downregulated proteins PDE-5, RhoA and increased expression of eNOS in the diabetic ED treated rats. The results obtained indicate that the methanolic extract of Maytenus procumbens roots ameliorates erectile dysfunction in type 2 diabetes-induced erectile dysfunction in rats.

scholarly journals Protective Effects of Orlistat on Lipid Profile, Cardiac Oxidative Stress Biomarkers and Histology in High-fat Diet-induced Obese Rats

2020 ◽  
Vol 18 (2) ◽  
Author(s):  
Othman ZA ◽  
Wan ghazali WS ◽  
Noordin L ◽  
Omar N ◽  
Mohd. Yusof NA ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
High Fat Diet ◽  
Male Rats ◽  
Protective Effects ◽  
Sprague Dawley ◽  
High Fat ◽  
Oxidative Stress Biomarkers ◽  
Stress Biomarkers ◽  
Obesity Index ◽  
Obese Rats

Introduction: Orlistat is a widely used drug in treating obesity as it promotes weight reduction. The aim of this study was to determine the protective effects of orlistat (10 mg/kg/day) on cardiovascular parameters and oxidative stress biomarkers in high-fat diet (HFD)-induced obese rats. Methods: Twenty-four male rats Sprague Dawley rats were divided into three groups and fed with normal diet (N), HFD and HFD with orlistat (HFD+O). Orlistat was administered daily by oral gavage and after six weeks, all rats were sacrificed. Results: Administration of orlistat along with HFD (HFD+O) has brought significant decreases in Lee obesity index and LDL level compared to HFD group. Activities of cardiac superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT) were significantly higher, whereas level of oxidised LDL was significantly lower in HFD+O group compared to HFD group. HFD group had significantly higher necrotic patch area in myocardium while minimal histological changes were seen in HFD+O group. Conclusion: This study may suggest that administration of orlistat at 10 mg/kg/day for 6 weeks may have protective effects against the changes on Lee obesity index, lipid profiles, cardiac oxidative stress biomarkers and histology of myocardium in HFD-induced obese rats possibly through its hypolipidaemic and antioxidant actions.

scholarly journals Maternal sitagliptin treatment attenuates offspring glucose metabolism and intestinal proinflammatory cytokines IL-6 and TNF-α expression in male rats

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e10310
Author(s):  
Qian Zhang ◽  
Xinhua Xiao ◽  
Jia Zheng ◽  
Ming Li ◽  
Miao Yu ◽  
...  
Keyword(s):  
Glucose Metabolism ◽  
Glucose Intolerance ◽  
Normal Diet ◽  
Male Rats ◽  
Male Rat ◽  
Sprague Dawley ◽  
Pregnant Rats ◽  
Tnf Α ◽  
Pregnancy And Lactation ◽  
Maternal Overnutrition

Increasing evidence shows that maternal overnutrition may increase the risk of diabetes in offspring. We hypothesized that maternal sitagliptin intervention may improve glucose intolerance through gut targeting. Female Sprague-Dawley (SD) rats were fed a normal diet (ND) or a high-fat diet (HFD) for 4 weeks before mating. ND pregnant rats were divided into two subgroups: ND group (ND alone) and the ND-sitagliptin group (ND combined with 10 mg/kg/day sitagliptin treatment). HFD pregnant rats were randomized to one of two groups: HFD group (HFD alone) and the HFD-sitagliptin group (HFD combined with 10 mg/kg/day sitagliptin treatment) during pregnancy and lactation. Glucose metabolism was assessed in offspring at weaning. Intestinal gene expression levels were investigated. Maternal sitagliptin intervention moderated glucose intolerance and insulin resistance in male pups. Moreover, maternal sitagliptin treatment inhibited offspring disordered intestinal expression of proinflammatory markers, including interleukin-6 (Il6), ll1b, and tumor necrosis factor (Tnf), at weaning and reduced intestinal IL-6, TNF-α expression by immunohistochemical staining and serum IL-6, TNF-α levels. However, maternal sitagliptin intervention did not affect offspring serum anti-inflammatory cytokine IL-10 level. Our results are the first to show that maternal sitagliptin intervention moderated glucose metabolism in male offspring. It may be involved with moderating intestinal IL-6 and TNF-α expression in male rat offspring.

scholarly journals Obese Zucker Rats Have Reduced Mineralocorticoid Receptor and 11β-Hydroxysteroid Dehydrogenase Type 1 Expression in Hippocampus—Implications for Dysregulation of the Hypothalamic-Pituitary-Adrenal Axis in Obesity

Endocrinology ◽  
2003 ◽  
Vol 144 (7) ◽  
pp. 2997-3003 ◽  
Author(s):  
Cecilia Mattsson ◽  
Maggie Lai ◽  
June Noble ◽  
Eoin McKinney ◽  
Joyce L. Yau ◽  
...  
Keyword(s):  
Hpa Axis ◽  
Glucocorticoid Receptors ◽  
Hydroxysteroid Dehydrogenase ◽  
Male Rats ◽  
Zucker Rats ◽  
Mrna Levels ◽  
Hypothalamic Pituitary Adrenal ◽  
Obese Rats ◽  
Obese Zucker Rats

Abstract Obese Zucker rats have elevated basal corticosterone levels and an increased stress response suggestive of an increased activity of the hypothalamic-pituitary-adrenal (HPA) axis. We hypothesized that altered central expression of glucocorticoid receptors (GR), mineralocorticoid receptors (MR), and/or 11β-hydroxysteroid dehydrogenase type 1 (11βHSD1) contribute to these changes. In brains from young adult male rats, in situ hybridization and Western blotting showed that obese rats had normal hippocampal GR mRNA and protein levels. In contrast, in obese rats, 11βHSD1 mRNA levels were reduced in a subpopulation of hippocampal cells in the main neuronal layers (by 37–47%, P < 0.05), whereas 11βHSD1 levels in sparse high-expressing cells did not differ. MR mRNA was decreased in all regions of the hippocampus (by 37–49%, P < 0.05 for CA1–2 and P < 0.01 for dentate gyrus) and in frontal cortex (by 16%, P < 0.05) in obese rats. In whole hippocampal homogenates, however, neither the protein concentration of MR by Western blot nor activity of 11βHSD1 was measurably different between the phenotypes. To test the functional importance of lower central MR expression, groups of lean and obese rats were given spironolactone before restraint stress. In vehicle-treated animals, obese rats had higher plasma corticosterone levels than lean rats after stress (by ANOVA, P < 0.05). Spironolactone markedly increased the corticosterone response in both groups, but the incremental rise was smaller in the obese rats, so that spironolactone abolished the differences between groups. We conclude that lower levels of MR, but not GR, contribute to the increased HPA activity in the obese Zucker rats and that this seems more influential during stress than in the basal state. This may be exacerbated by impaired local regeneration of corticosterone by 11βHSD1. These abnormalities could contribute to the subtle changes in the HPA axis in rodent and human obesity.

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