kiss1-protein--human and Insulin-Resistance

Age is a major risk factor for developing metabolic diseases such as obesity and diabetes. There is an unprecedented rise in obesity and type 2 diabetes in recent decades. A convincing majority of brain-gut peptides are associated with a higher risk to develop metabolic disorders, and may contribute to the pathophysiology of age-related metabolic diseases. Accumulating basic studies revealed an intriguing role of kisspeptin and galanin involved in the amelioration of insulin resistance in different ways. In patients suffered from obesity and diabetes a significant, sex-related changes in the plasma kisspeptin and galanin levels occurred. Kisspeptin is anorexigenic to prevent obesity, its level is negatively correlative with obesity and insulin resistance. While galanin is appetitive to stimulate food intake and body weight, its level is positively correlative with obesity, HOMA-IR and glucose/triglyceride concentration. In turn, kisspeptin and galanin also distinctly increase glucose uptake and utilization as well as energy expenditure. This article reviews recent evidence dealing with the role of kisspeptin and galanin in the pathophysiology of age-related metabolic diseases. It should be therefore taken into account that the targeted modulation of those peptidergic signaling may be potentially helpful in the future treatment of age-related metabolic diseases.

Topics: Aging; Animals; Diabetes Mellitus, Type 2; Drug Discovery; Galanin; Humans; Insulin Resistance; Kisspeptins; Obesity; Signal Transduction

This systematic review and meta-analysis aimed to summarize the available evidence regarding circulating kisspeptin and anti-müllerian hormone (AMH) and the homeostasis model assessment of insulin resistance (HOMA-IR) index in adolescents and women with and without polycystic ovary syndrome (PCOS).. We performed a comprehensive literature search in Medline, Embase, Cochrane, Scopus, and Web of Science for studies evaluating circulating kisspeptin levels in women with and without PCOS published until September 24th, 2020. Co-primary outcomes were the HOMA-IR index and AMH. The quality of included studies was assessed using the Newcastle-Ottawa Scale. Random-effects models were used to estimate outcomes, and effects reported as mean difference (MD) or standardized MD (SMD) and their 95 % confidence interval (CI). The systematic review and meta-analysis was registered in the International Prospective Register of Systematic Reviews (PROSPERO) as number CRD42020205030.. We evaluated 18 studies including, 1282 PCOS cases and 977 controls. Participants with PCOS were younger (MD = -2.38 years, 95 %CI -4.32 to -0.44), with higher BMI (MD = 1.16, 95 % CI 0.54-1.78), waist-to-hip ratio (MD = 0.04, 95 %CI 0.02 to 0.05), circulating kisspeptin (SMD = 1.15, 95 %CI 0.68-1.62), luteinizing hormone (SMD = 1.29, 95 %CI 0.76-1.83), AMH (SMD = 0.97, 95 %CI 0.60-1,34), total testosterone (SMD = 2.48, 95 %CI 1.73-3.23), free testosterone (SMD = 1.37, 95 %CI 0.56-2.17), and dehydroepiandrosterone sulphate (SMD = 0.72, 95 %CI 0.32-1.13) levels, and Ferriman-Gallwey score (SMD = 5.08, 95 %CI 2.76-7.39), and lower sex hormone-binding globulin level (SMD = -1.34, 95 %CI -2.15 to -0.52). Besides, participants with PCOS had higher HOMA-IR index (SMD = 0.76, 95 %CI 0.35-1.17), and circulating insulin (SMD = 0.75, 95 %CI 0.30-1.19), leptin (SMD = 2.82, 95 %CI 1.35-4.29), and triglycerides (SMD = 2.15, 95 %CI 1.08-3.23) levels than participants without the syndrome. The meta-regression did not identify significant factors influencing circulating kisspeptin.. Patients with PCOS showed higher kisspeptin, LH, insulin, AMH, and androgen levels and HOMA-IR index, and lower sex hormone-binding globulin levels than those without the syndrome.

Topics: Adolescent; Anti-Mullerian Hormone; Female; Humans; Insulin Resistance; Kisspeptins; Polycystic Ovary Syndrome

Non-alcoholic fatty liver disease (NAFLD) adversely affects reproduction. We aimed to study the effect of a high-fat diet (HFD), supplemented with apple vinegar, on folliculogenesis in a rat model of NAFLD.. Female rats were randomly divided into four groups (N = 28): Standard diet (SD), SD + vinegar, HFD, and HFD + vinegar groups. At the end of the study, biochemical tests were assessed in serum. HOMA-IR (Homeostatic model assessment-Insulin resistance) was calculated. Sex hormones were determined using an ELISA kit; ovary follicle counts were studied using histological methods. The proliferation index of granulosa cells was determined using immunohistochemistry. Kisspeptin expression in the ovary was detected using RT-PCR.. The HFD induced steatohepatitis and NAFLD. The ovaries in the rat model of NAFLD were atrophied. The ovaries had less count of developing follicles and corpus luteum, and more degenerated and cystic follicles in comparison with the SD group. Vinegar + HFD consumption decreased ALT, compared to the HFD group (P = 0.004). Steatohepatitis was reduced in the Vinegar + HFD group (P = 0.001). Vinegar + HFD considerably reduced HOMA-IR (p = 0.01). The HFD + vinegar diet could increase estradiol (P = 0.001), without significantly affecting progesterone or testosterone. In addition, an increase of primordial follicles as an ovarian reserve and also primary follicles were determined in the HFD + vinegar group. There were no statistical differences in the granulosa cell proliferation index in various follicle types between groups. HFD + vinegar significantly enhanced ovarian kisspeptin expression (p = 0.04).. The vinegar diet in a rat model of NAFLD raises estradiol, primordial, and small primary follicles, and increases ovarian kisspeptin expression indirectly. Insulin resistance and obesity were improved by apple vinegar, and anti-glycemic and anti-lipidemic effects were also determined. The supplementation of apple vinegar in NAFLD might be useful for ovary. However, it requires further investigation.

Topics: Acetic Acid; Animals; Diet, High-Fat; Estradiol; Female; Insulin Resistance; Kisspeptins; Liver; Malus; Non-alcoholic Fatty Liver Disease; Ovary; Rats

Central kisspeptin action is well known in reproductive regulation; however, its peripheral action is not well understood. This study aimed to 1) compare serum or cerebrospinal fluid (CSF) kisspeptin levels between different body mass index (BMI) groups 2) compare the levels of kisspeptin between serum and CSF, and 3) determine correlations between serum or CSF kisspeptin levels with clinical, metabolic, and reproductive parameters. There were 40 male subjects undergoing operations with lumbar puncture anesthesia. Subgroup analysis was performed to compare between the normal (n = 12), overweight (n = 10), and obese groups (n = 17). One lean subject was recruited for correlation analysis. Serum kisspeptin levels were significantly higher in the obese group when compared to the normal weight and overweight groups even after adjusting for age or diastolic blood pressure (DBP) (p < 0.05 all). Serum leptin levels were significantly higher in the obese group when compared to the normal weight and overweight groups (p < 0.05 all). CSF kisspeptin levels were below the minimum detectable concentration for the assay (<0.06 ng/mL). Serum kisspeptin was positively correlated with body weight, BMI, plasma insulin, the homeostatic model assessment for insulin resistance (HOMA-IR), and serum leptin but was negatively correlated with plasma LH (p < 0.05 all). In conclusion, serum kisspeptin was related to obesity, leptin, insulin, and insulin resistance, while CSF kisspeptin was below the limits of detection. Thus, peripheral kisspeptin might have a role in metabolic regulation.

Topics: Adult; Anesthesia; Body Mass Index; Body Weight; Female; Humans; Insulin Resistance; Kisspeptins; Leptin; Male; Obesity; Overweight; Reproduction; Spinal Puncture

Kisspeptin, neuropeptide involved in puberty beginning and regulation of pituitary-gonadal axis, has been shown to stimulate antioxidant defenses in murine models. Its levels are greater in females than males and also in obese prepubertal girls. Therefore, our aim was to evaluate sex-related differences in prepubertal obese patients and the relationships of Kisspeptin with metabolic/hormonal parameters.. We studied Kisspeptin concentrations in 54 children (22 males and 32 females, Tanner stage 1), 5-12 ys, classified according to Cole's criteria into 17 overweight and 37 obese; 25 normal-weight children, aged 6-12 years, were studied as controls. We evaluated metabolic (glucose and insulin levels after oral glucose load, total- LDL- HDL-cholesterol, triglycerides, uric acid) and hormonal (fT3, fT4, TSH, IGF-1, leptin) parameters. Moreover, total antioxidant capacity (TAC) was evaluated by spectrophotometric method, using the system H202-metmyoglobin-ABTS. Kisspeptin levels were measured by RIA.. We did not find significant differences between obese and normal-weight children, but obese males presented significantly lower levels than females. Kisspeptin did not correlate with BMI, HOMA-IR, Insulin peak levels and TAC; a significant correlation was found between Kisspeptin and fT3 (r2=0.25; p=0.003) in the obese group; leptin levels, significantly greater in obese vs. overweight and control children, significantly correlated with TAC (r2=0.39; p=0.03).. These data suggest that both hormones could modulate antioxidants, Kisspeptin indirectly via influence on thyroid hormones, and Leptin by a direct effect. This mechanism seems to be sex-related, not attributable to peripheral steroid levels. Further studies can clarify the complex interrelationship between central and peripheral Kisspeptin secretion and oxidative stress in children obesity.

Topics: Antioxidants; Body Mass Index; Case-Control Studies; Child; Child, Preschool; Female; Humans; Insulin Resistance; Kisspeptins; Leptin; Male; Pediatric Obesity; Sex Characteristics; Spectrophotometry

Eucommia ulmoides Oliv. leaves are the dry leaves of Eucommia ulmoides Oliv. Modern studies have shown that Eucommia ulmoides Oliv. leaves and its extracts have many pharmacological effects, such as regulating hypothalamus pituitary ovary (HPO) axis function, estrogen like effects, correcting insulin resistance (IR), regulating lipids, and reducing weight, which are consistent with the clinical manifestations in polycystic ovary syndrome (PCOS) patients. PCOS patients often have HPO axis disorder, low estrogen, high androgen, high IR complication rate, and obesity. Previous preclinical studies have shown that total flavonoids from Eucommia ulmoides Oliv. leaves (TFEL) can improve the imbalance in sex hormone secretion in perimenopausal animal models by regulating the function of the HPO axis. Thus, it is important to understand if flavonoids are the active parts of Eucommia ulmoides Oliv. leaves that interfere with polycystic ovary syndrome with insulin resistance (PCOS-IR), and determine the regulatory role they play in sex hormones and IR?. Investigate the phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signaling pathway in the ovary and kisspeptin/insulin like growth factor/leptin receptor1/androgen receptor (Kiss1/IGF-1/LEPR/AR) in the HPO axis to determine the mechanism of TFEL intervention in a rat model of PCOS-IR model rats.. A rat model of PCOS-IR was established using a high-fat diet (49 d) combined with letrozole (1 mg/kg·d, for 28 d). Then, metformin (300 mg/kg·d) and TFEL (220 mg/kg·d, 110 mg/kg·d, and 55 mg/kg·d) were administered continuously for 21 days. At the end of the experiment, samples were taken and the related indexes were measured.. TFEL reduced the body weight, Lee's index, ovarian index, ovarian area and ovarian volume, increased serum E. TFEL can inhibit ovarian hyperplasia, regulate disorders of glucose and lipid metabolism and improve the secretion of sex hormones, by regulating the expression of PI3K/AKT signaling pathway-related proteins in the ovary and Kiss1/IGF-1/LEPR/AR in the HPO axis.

Topics: Animals; Body Weight; Diet, High-Fat; Disease Models, Animal; Eucommiaceae; Female; Flavonoids; Gonadal Steroid Hormones; Hypothalamus; Insulin Resistance; Insulin-Like Growth Factor I; Kisspeptins; Letrozole; Metformin; Ovary; Pancreas; Phosphatidylinositol 3-Kinases; Pituitary Gland; Plant Extracts; Plant Leaves; Polycystic Ovary Syndrome; Proto-Oncogene Proteins c-akt; Rats, Sprague-Dawley; Receptors, Androgen; Receptors, Leptin

Both obesity and diabetes play a significant role in reproductive disorders in women and insulin resistance (IR) is a confirmed. We recruited 32 female youths: 14 of them presented with T1D (14.6 ± 2.6 years) and 18 with obesity (15.1 ± 2.6 years). The control group included 20 age-matched normal weight females. Each patient underwent physical examination and hormonal assessment. AMH, kisspeptin and adiponectin levels were also measured. IR was calculated as the homeostasis model assessment for insulin resistance (HOMA-IR) and the glucose disposal rate (eGDR) in patients with obesity and with T1D, respectively.. adiponectin and kisspeptin levels were significantly different into groups (. IR displays a relationship with adiponectin and kisspeptin in young reproductive-aged women with obesity and T1D. Interventions to correct IR in adolescents could be part of an early approach to prevent reproductive disorders and to promote factors associated with longevity in adult women.

Topics: Adiponectin; Adolescent; Anti-Mullerian Hormone; Biomarkers; Body Mass Index; Diabetes Mellitus, Type 1; Female; Humans; Insulin Resistance; Kisspeptins; Obesity; Ovarian Reserve; Young Adult

Endoplasmic reticulum (ER) stress, with adaptive unfolded protein response (UPR), is a key link between obesity, insulin resistance and type 2 diabetes, all of which are often present in the most common endocrine-metabolic disorder in women of reproductive age, polycystic ovary syndrome (PCOS), which is characterized with hyperandrogenism. However, the link between excess androgen and endoplasmic reticulum (ER) stress/insulin resistance in patients with polycystic ovary syndrome (PCOS) is unknown. An unexpected role of kisspeptin was reported in the regulation of UPR pathways and its involvement in the androgen-induced ER stress in hypothalamic neuronal cells. To evaluate the relationship of kisspeptin and ER stress, we detected kisspeptin and other factors in blood plasm of PCOS patients, rat models and hypothalamic neuronal cells. We detected higher testosterone and lower kisspeptin levels in the plasma of PCOS than that in non-PCOS women. We established a PCOS rat model by dihydrotestosterone (DHT) chronic exposure, and observed significantly downregulated kisspeptin expression and activated UPR pathways in PCOS rat hypothalamus compared to that in controls. Inhibition or knockdown of kisspeptin completely mimicked the enhancing effect of DHT on UPR pathways in a hypothalamic neuronal cell line, GT1-7. Kp10, the most potent peptide of kisspeptin, effectively reversed or suppressed the activated UPR pathways induced by DHT or thapsigargin, an ER stress activator, in GT1-7 cells, as well as in the hypothalamus in PCOS rats. Similarly, kisspeptin attenuated thapsigargin-induced Ca

Topics: Androgens; Animals; Diabetes Mellitus, Type 2; Disease Models, Animal; Endoplasmic Reticulum; Endoplasmic Reticulum Stress; Female; Hypothalamus; Insulin Resistance; Kisspeptins; Neurons; Obesity; Polycystic Ovary Syndrome; Rats; Testosterone; Unfolded Protein Response

Hypogonadism and oxidative stress are occurring commonly in men with diabetes and associated male infertility. This study aimed to investigate the capability of anti-oxidative and anti-inflammatory properties of fucoxanthin as well as to evaluate its protective effects on male reproduction in diabetic rats. The RAW 264.7 macrophage cells were used to evaluate the anti-oxidative and anti-inflammatory activity. Thirty male Sprague-Dawley rats were induced by streptozotocin-nicotinamide for a diabetes model and fed either with three different doses of fucoxanthin (13, 26, and 65 mg/kg) or rosiglitazone (0.571 mg/kg) for four weeks. The fucoxanthin significantly inhibited nitric oxide production and reduced reactive oxygen species level in lipopolysaccharide-induced RAW 264.7 cells. In the animal study, fucoxanthin administration improved insulin resistance, restored sperm motility, decreased abnormal sperm number, and inhibited lipid peroxidation. Moreover, it restored GPR54 and SOCS-3 mRNA expression in the hypothalamus and recovered luteinizing hormone level, as well as the testosterone level. In conclusion, fucoxanthin not only possessed antioxidant and anti-inflammatory properties but also decreased the diabetes signs and symptoms as well as improved spermatogenesis and male reproductive function.

Topics: Animals; Antioxidants; Blood Glucose; Cell Survival; Diabetes Mellitus, Experimental; Disease Models, Animal; Inflammation Mediators; Insulin; Insulin Resistance; Kisspeptins; Male; Malondialdehyde; Mice; Niacinamide; Nitric Oxide; Oxidative Stress; Phaeophyceae; Rats, Sprague-Dawley; RAW 264.7 Cells; Reactive Oxygen Species; Receptors, Kisspeptin-1; Reproduction; RNA, Messenger; Spermatozoa; Streptozocin; Suppressor of Cytokine Signaling 3 Protein; Testis; Xanthophylls

Spexin (SPX) and kisspeptin (KISS) are novel peptides relevant in the context of regulation of metabolism, food intake, puberty and reproduction. Here, we studied changes of serum SPX and KISS levels in female non-obese volunteers (BMI<25 kg/m(2)) and obese patients (BMI>35 kg/m(2)). Correlations between SPX or KISS with BMI, McAuley index, QUICKI, HOMA IR, serum levels of insulin, glucagon, leptin, adiponectin, orexin-A, obestatin, ghrelin and GLP-1 were assessed. Obese patients had lower SPX and KISS levels as compared to non-obese volunteers (SPX: 4.48+/-0.19 ng/ml vs. 6.63+/-0.29 ng/ml; p<0.001, KISS: 1.357+/-0.15 nmol/l vs. 2.165+/-0.174 nmol/l; p<0.01). SPX negatively correlated with BMI, HOMA-IR, insulin, glucagon, active ghrelin and leptin. Positive correlations were found between SPX and QUICKI index, McAuley index, serum levels of obestatin, GLP-1 and adiponectin and orexin-A Serum KISS negatively correlated with BMI, HOMA-IR, serum levels of insulin, glucagon, active ghrelin and leptin. KISS positively correlated with QUICKI index, McAuley index and adiponectin. In summary, SPX and KISS show negative correlations with obesity, insulin resistance indices, and hormones known to affect insulin sensitivity in females. Both, SPX and KISS could be therefore relevant in the pathophysiology of obesity and insulin resistance.

Topics: Adult; Biomarkers; Female; Humans; Insulin Resistance; Kisspeptins; Middle Aged; Obesity; Peptide Hormones

Male hypogonadism is defined as the deficiency of testosterone or sperm production synthesized by testicles or the deficiency of both. The reasons for hypogonadism may be primary, meaning testicular or secondary, meaning hypothalamohypophyseal. In hypogonadotropic hypogonadism (HH), there is indeficiency in gonadotropic hormones due to hypothalamic or hypophyseal reasons. Gonadotropin-releasing hormone (GnRH) is an important stimulant in releasing follicular stimulant hormone (FSH), mainly luteinizing hormone (LH). GnRH omitted is under the effect of many hormonal or stimulating factors. Kisspeptin is present in many places of the body, mostly in hypothalamic anteroventral periventricular nucleus and arcuate nucleus. Kisspeptin has a suppressor effect on the metastasis of many tumors such as breast cancer and malign melanoma metastases, and is called "metastin" for this reason. Kisspeptin is a strong stimulant of GnRH. In idiopathic hypogonadotropic hypogonadism (IHH) etiology, there is gonadotropic hormone release indeficiency which cannot be clearly described. A total of 30 male hypogonatropic hypogonadism diagnosed patients over 30 years of age who have applied to Haydarpasa Education Hospital Endocrinology and Metabolic Diseases Service were included in the study. Compared to the control group, the effect of kisspeptin on male patients with hypogonatropic hypogonadism and on insulin resistance developing in hypogonadism patients was investigated in our study. A statistically significant difference was detected between average kisspeptin measurements of the groups (p < 0.01). Kisspeptin measurement of the cases in the patient group were detected significantly high. No statistically significant relation was detected among kisspeptin and LH/FSH levels. Although a positive low relation was detected between kisspeptin measurements of patient group cases and homeostasis model assessment of insulin resistance (HOMA-IR) measurements, this relation was statistically insignificant. When the patient and control groups were compared for HOMA-IR, no statistically significant difference was detected. The reason for high kisspeptin levels in the patient group compared to the control group makes us consider that there may be a GPR54 resistance or GnRH neuronal transfer pathway defect. When patients and control groups were compared for HOMA-IR, the difference was not statistically significant. It is considered that kisspeptin is one of the reasons for hypogonatropic h

Topics: Adult; Humans; Hypogonadism; Insulin Resistance; Kisspeptins; Male; Young Adult

The aim of the present study was to evaluate serum concentrations of metastin in relation with hormonal and metabolic profile in patients with and without polycystic ovary syndrome (PCOS).. The study was a clinical study. Eighty-three women with PCOS and 66 body mass index (BMI) matched controls were divided into two groups, based on BMI: overweight and obese (BMI≥25 kg/m(2)) and normal weight. (BMI<25 kg/m(2)) Hirsutism scores, hormonal and metabolic profile as well as metastin levels were evaluated in each subject. Blood samples were collected in the early follicular phase (between day 2 and day 5 of the menstrual cycle) at 9:00 AM, after an overnight fast. Circulating levels of LH, FSH, PRL, TSH, T, fT, DHEAS, 17-OH-P, sex hormone-binding globulin (SHBG), insulin, glucose, lipid profile and metastin were measured.. Metastin levels were significantly higher in the PCOS group compared to controls (2.02 ng/ml versus 1.16 ng/ml, p<0.001). Metastin levels correlated significantly positively with luteinizing hormone (LH), total testosterone (T), dehydroepiandrosteronesulphate (DHEA-SO4) levels, modified Ferriman-Gallwey (mFG) scores and free androgen index (FAI); however, correlated negatively with sex hormone binding globulin (SHBG) levels (p<0.05). When overweight or obese (BMI≥25 kg/m(2)) and normal weight (BMI<25 kg/m(2)) women with PCOS were compared to body mass index (BMI) matched controls, higher metastin levels were also found in PCOS groups (1.94 ng/ml versus 1.18 ng/ml, and 2.06 ng/ml versus 1.08 ng/ml, p<0.05, respectively).. These findings suggest that metastin levels were higher in women with PCOS as compared to controls regardless of BMI. Furthermore, metastin levels can be used as a specific marker for androgenic profile and this marker might play a role in the pathogenesis of PCOS.

Topics: Adolescent; Adult; Blood Glucose; Case-Control Studies; Dehydroepiandrosterone Sulfate; Female; Follicle Stimulating Hormone; Hirsutism; Humans; Insulin Resistance; Kisspeptins; Lipids; Luteinizing Hormone; Obesity; Overweight; Polycystic Ovary Syndrome; Prolactin; Sex Hormone-Binding Globulin; Testosterone; Thyrotropin; Young Adult

This study was designed to: [1] measure, for the first time, metastin (kisspeptin) levels in women with polycystic ovary syndrome (PCOS), a condition associated with hypersecretion of LH and hyperandrogenemia; and [2] investigate the possible correlations between metastin and PCOS-related reproductive and metabolic disturbances.. Clinical study.. University hospital.. Twenty-eight obese and overweight (body mass index [BMI] >25 kg/m2) women with PCOS, 28 normal weight (BMI <25 kg/m2) women with the syndrome, and 13 obese and overweight controls (ovulatory women without clinical or biochemical hyperandrogenemia) were selected.. Blood samples were collected between day 3 and day 6 of a spontaneous bleeding episode in the PCOS groups and a menstrual cycle of the controls, at 9:00 AM, after an overnight fast.. Circulating levels of LH, FSH, PRL, T, Delta4-androstenedione (A), DHEAS, 17alpha-OH-P, sex hormone-binding globulin (SHBG), insulin, glucose, and metastin were measured.. Both normal weight women with PCOS and obese controls were less insulin resistant and had significantly higher metastin levels, compared to obese and overweight women with the syndrome. Plasma kisspeptin levels were negatively correlated with BMI, free androgen index, and indices of insulin resistance.. These results indicate that metastin is negatively associated with free androgen levels. The PCOS-associated insulin resistance and consequent hyperinsulinemia probably contribute to this effect by [1] stimulating androgen synthesis by the polycystic ovary (PCO) and [2] suppressing SHBG production in the liver.

Topics: Adolescent; Adult; Androgens; Biomarkers; Female; Greece; Humans; Insulin; Insulin Resistance; Kisspeptins; Obesity; Polycystic Ovary Syndrome; Statistics as Topic; Tumor Suppressor Proteins