Spexin Diminishes Atrial Fibrillation Vulnerability by Acting on Galanin Receptor 2.

BACKGROUND: G protein-coupled receptors play a critical role in atrial fibrillation (AF). Spexin is a novel ligand of galanin receptors (GALRs). In this study, we investigated the regulation of spexin and GALRs on AF and the underlying mechanisms. METHODS: Global spexin knockout (SPX-KO) and cardiomyocyte-specific GALRs knockout (GALR-cKO) mice underwent burst pacing electrical stimulation. Optical mapping was used to determine atrial conduction velocity and action potential duration. Atrial myocyte action potential duration and inward rectifying K+ current (IK1) were recorded using whole-cell patch clamps. Isolated cardiomyocytes were stained with Fluo-3/AM dye, and intracellular Ca2+ handling was examined by CCD camera. A mouse model of AF was established by Ang-II (angiotensin II) infusion. RESULTS: Spexin plasma levels in patients with AF were lower than those in subjects without AF, and knockout of spexin increased AF susceptibility in mice. In the atrium of SPX-KO mice, potassium inwardly rectifying channel subfamily J member 2 (KCNJ2) and sarcolipin (SLN) were upregulated; meanwhile, IK1 current was increased and Ca2+ handling was impaired in isolated atrial myocytes of SPX-KO mice. GALR2-cKO mice, but not GALR1-cKO and GALR3-cKO mice, had a higher incidence of AF, which was associated with higher IK1 current and intracellular Ca2+ overload. The phosphorylation level of CREB (cyclic AMP responsive element binding protein 1) was upregulated in atrial tissues of SPX-KO and GALR2-cKO mice. Chromatin immunoprecipitation confirmed the recruitment of p-CREB to the proximal promoter regions of KCNJ2 and SLN. Finally, spexin treatment suppressed CREB signaling, decreased IK1 current and decreased intracellular Ca2+ overload, which thus reduced the inducibility of AF in Ang-II-infused mice. CONCLUSIONS: Spexin reduces atrial fibrillation susceptibility by inhibiting CREB phosphorylation and thus downregulating KCNJ2 and SLN transcription by GALR2 receptor. The spexin/GALR2/CREB signaling pathway represents a novel therapeutic avenue in the development of agents against atrial fibrillation.

Exercise Training and Spexin Ameliorate Thyroid Changes in Obese Type 2-Diabetic Rats: The Possible Interlaying Mechanisms.

Thyroid dysfunction and diabetes mellitus are prevalent endocrine disorders that often coexist and influence each other. The role of spexin (SPX) in diabetes and obesity is well-documented, but its connection to thyroid function is less understood. This study investigates the influence of exercise (EX) and SPX on thyroid hypofunction in obese type 2 diabetic rats. Rats were divided into normal control, obese diabetic sedentary, obese diabetic EX, and obese diabetic SPX groups, with subdivisions for M871, and HT-2157 treatment in the later 2 groups. High-fat diet together with streptozotocin injection induced obesity and diabetes. The EX-group underwent swimming, while the SPX-group received SPX injections for eight weeks. Results showed significant improvements in thyroid function, metabolic, oxidative, and inflammatory states with EX and SPX-treatment. The study also explored the involvement of galanin receptor isoforms (GALR) 2/3 in SPX effects on thyroid function. Blocking GALR2/3 receptors partially attenuated the beneficial effects, indicating their interaction. These findings underscore the importance of EX and SPX in modulating thyroid function in obesity and diabetes. Comprehending this interplay could enable the development of new treatment approaches for thyroid disorders associated with obese type 2 diabetes. Additional research is necessary to clarify the exact mechanisms connecting SPX, EX activity, and thyroid function.

Spexin acts as a novel glucose-lowering factor in grass carp (Ctenopharyngodon idella).

At present, the physiological roles of various hormones in fish glucose metabolism have been elucidated. Spexin, a 14-amino acids polypeptide, is highly conserved in many species and has functions such as reducing body weight and improving insulin resistance. In this paper, the open reading frame (ORF) of spx21 in grass carp (Ctenopharyngodon idella) was cloned, and the tissue distribution of spx1 and spx2, their direct and indirect regulatory effects on glucose metabolism of grass carp were investigated. The ORF of spx2 gene in grass carp was 279 bp in length. Moreover, spx1 was highly expressed in the adipose tissue, while spx2 was highly expressed in the brain. In vitro, SPX1 and SPX2 showed opposite effects on the glycolytic pathway in the primary hepatocytes. In vivo, intraperitoneal injection of SPX1 and SPX2 significantly reduced serum glucose levels and increased hepatopancreas glycogen contents. Meanwhile, SPX1 and SPX2 promoted the expression of key genes of glycolysis (pk) and glycogen synthesis (gys) in the hepatopancreas at 3 h post injection. As for indirect effects, 1000 nM SPX1 and SPX2 significantly increased insulin-mediated liver type phosphofructokinase (pfkla) mRNA expression and enhanced the inhibitory effects of insulin on glucose-6-phosphatase (g6pase), phosphoenolpyruvate carboxykinase (pepck), glycogen phosphorylase L (pygl) mRNA expression. Our results show that SPX1 and SPX2 have similar indirect effects on the regulation of glucose metabolism that enhance insulin activity, but they exhibit opposite roles in terms of direct effects.

The Investigation of Kisspeptin, Spexin and Galanin in Euthyroid Women with Hashimoto's Thyroiditis.

OBJECTIVE: The hallmarks of Hashimoto's thyroiditis (HT) include the destruction of thyroid cells by leading to insulin resistance (IR), hypothyroidism, and metabolic abnormalities. Kisspeptin, spexin, and galanin control appetite and body weight (BW) to regulate metabolisms. Here, we sought to determine if galanin, kisspeptin, and spexin are linked to the pathophysiology of HT in euthyroid female individuals. METHODS: Forty-five women with HT and 45 healthy control women of the same age participated in the current study. The enzyme-linked immunosorbent assay (ELISA) method was used to measure the serum levels of galanin, spexin, and kisspeptin. RESULTS: In comparison to the controls, HT patients had significantly higher levels of kisspeptin (p < 0.01), galanin (p < 0.01), anti-thyroid peroxidase (anti-TPO) (p < 0.001), anti-thyroglobulin (anti-Tg) (p < 0.001), and body mass index (BMI) (p < 0.05). The two groups were comparable in terms of spexin, free triiodothyronine-3 (fT3), fT4, thyroid-stimulating hormone (TSH) levels, and homeostatic model assessment for insulin resistance (HOMA-IR). Galanin and kisspeptin were seen to have a positive correlation (p < 0.01; r = 0.786). CONCLUSIONS: Euthyroid women with HT were found to have higher levels of kisspeptin and galanin. These results imply that kisspeptin and galanin may be linked to the pathogenesis of hypothyroidism, and as a result, we believe that these markers may be beneficial in the early detection and treatment of HT patients.

Role of Spexin in White Adipose Tissue Thermogenesis under Basal and Cold-Stimulated Conditions.

Spexin (SPX) is a novel adipokine that plays an emerging role in metabolic diseases due to its involvement in carbohydrate homeostasis, weight loss, appetite control, and gastrointestinal movement, among others. In obese patients, SPX plasma levels are reduced. Little is known about the relationship between SPX and white adipose tissue (WAT) thermogenesis. Therefore, the aim of the present study was to evaluate the role of SPX in this process. C57BL/6J male mice were treated or not with SPX for ten days. On day 3, mice were randomly divided into two groups: one kept at room temperature and the other kept at cold temperature (4 °C). Caloric intake and body weight were recorded daily. At the end of the protocol, plasma, abdominal (epididymal), subcutaneous (inguinal), and brown AT (EAT, IAT, and BAT, respectively) depots were collected for measurements. We found that SPX treatment reduced Uncoupling protein 1 levels in WAT under both basal and cold conditions. SPX also reduced cox8b and pgc1α mRNA levels and mitochondrial DNA, principally in IAT. SPX did not modulate the number of beige precursors. SPX decreased spx levels in IAT depots and galr2 in WAT depots. No differences were observed in the BAT depots. In conclusion, we showed, for the first time, that SPX treatment in vivo reduced the thermogenic process in subcutaneous and abdominal AT, being more evident under cold stimulation.

Spexin role in human granulosa cells physiology and PCOS: expression and negative impact on steroidogenesis and proliferation†.

Spexin (SPX) is a novel neuropeptide and adipokine negatively correlated with obesity and insulin resistance. A recent study investigated expression and regulatory function of SPX in the hypothalamus and pituitary; however, the effect on ovarian function is still unknown. The aim of this study was to characterize the expression of SPX and its receptors, galanin receptors 2 and 3 (GALR2/3), in the human ovary and to study its in vitro effect on granulosa cells (GC) function. Follicular fluid (FF) and GC were obtained from normal weight and obese healthy and diagnosed with polycystic ovarian syndrome (PCOS) women. Expression of SPX and GALR2/3 in the ovary was studied by qPCR, western blot, and immunohistochemistry. The level of SPX in FF was assessed by enzyme-linked immunosorbent assay. The in vitro effect of recombinant human SPX on GC proliferation, steroidogenesis, and signaling pathways (MAP3/1, STAT3, AKT, PKA) was analyzed. Moreover, GC proliferation and estradiol (E2) secretion were measured with and without an siRNA against GALR2/3 and pharmacological inhibition of the above kinases. The results showed that both the SPX concentration in FF and its gene expression were decreased in GC of obese and PCOS women, while the protein expression of GALR2/3 was increased. We noted that SPX reduced GC proliferation and steroidogenesis; these effects were mediated by GALR2/3 and kinases MAP3/1, AKT, and STAT3 for proliferation or kinases MAP3/1 and PKA for E2 secretion. The obtained data clearly documented that SPX is a novel regulator of human ovarian physiology and possibly plays a role in PCOS pathogenesis.

Evaluation of the adipokine levels of pregnant women with preeclampsia.

AIM: The aim of this study was to compare maternal blood and umbilical-cord leptin, spexin and visfatin levels during delivery in severe preeclampsia (PE) with controls, and to evaluate whether any clinical or demographic variables had independent associations with them. METHODS: This is a case-controlled observational study consisting of 45 pregnant women with severe PE and a control group consisting of gestational age-matched 45 healthy pregnant women. We examined the leptin, spexin, and visfatin levels in serum samples taken from maternal blood and umbilical cords during cesarean section in both groups. Leptin, spexin, and visfatin levels were measured by enzyme-linked immunosorbent assay. RESULTS: The maternal leptin and visfatin levels were significantly higher and the maternal spexin levels were significantly lower in the PE group than in the control group (p < 0.001). Similar to the maternal adipokine levels, the umbilical-cord leptin and visfatin levels were significantly higher and the spexin levels were significantly lower in the PE group (p < 0.001). We found a significant positive correlation between maternal body mass index and maternal blood and umbilical-cord serum leptin and visfatin levels in both groups (p < 0.001). CONCLUSION: The leptin, spexin and visfatin levels were significantly altered in the nondiabetic preeclamptic women in our study. We believe that the main reason for these changes may be the hypoxic placenta to protect the fetus and maintain its nutrition.

Spexin2 Is a Novel Food Regulator in Gallus gallus.

Spexin2 (SPX2), a paralog of SPX1, is a newly identified gene in non-mammalian vertebrates. Limited studies in fish have evidenced its important role in food intake and energy balance modulation. However, little is known about its biological functions in birds. Using the chicken (c-) as a model, we cloned the full-length cDNA of SPX2 by using RACE-PCR. It is 1189 base pair (bp) in length and predicted to generate a protein of 75 amino acids that contains a 14 amino acids mature peptide. Tissue distribution analysis showed that cSPX2 transcripts were detected in a wide array of tissues, with abundant expression in the pituitary, testis, and adrenal gland. cSPX2 was also observed to be ubiquitously expressed in chicken brain regions, with the highest expression in the hypothalamus. Its expression was significantly upregulated in the hypothalamus after 24 or 36 h of food deprivation, and the feeding behavior of chicks was obviously suppressed after peripheral injection with cSPX2. Mechanistically, further studies evidenced that cSPX2 acts as a satiety factor via upregulating cocaine and amphetamine regulated transcript (CART) and downregulating agouti-related neuropeptide (AGRP) in hypothalamus. Using a pGL4-SRE-luciferase reporter system, cSPX2 was demonstrated to effectively activate a chicken galanin II type receptor (cGALR2), a cGALR2-like receptor (cGALR2L), and a galanin III type receptor (cGALR3), with the highest binding affinity for cGALR2L. Collectively, we firstly identified that cSPX2 serves as a novel appetite monitor in chicken. Our findings will help clarify the physiological functions of SPX2 in birds as well as its functional evolution in vertebrates.

Levels of spexin and its receptors GALR2 and GALR3 in the hypothalamus and ovary of letrozole-induced polycystic ovary syndrome in rats.

Spexin (SPX) is a newly identified neuropeptide, a natural ligand for the galanin receptors (GALR) 2/3, which is involved in maintaining physiological functions including female reproduction. One of the most common endocrine disorder in reproductive system is polycystic ovary syndrome (PCOS), however the role of SPX in PCOS is still unknown. The objective of this study was to determine the expression of mRNA and peptide levels of SPX and its receptors GALR2/3 in the hypothalamus and ovary (by real time PCR and Western blot) as well as plasma levels of SPX (ELISA) in letrozole - induced PCOS rats. We observed that SPX plasma level does not change in PCOS rats. In the hypothalamus transcript level of Spx and Galr3 were significantly higher in PCOS rats compared to the control, while mRNA of Galr2 and protein expression of GALR2/3 were lower. Moreover, expression of Spx and Galr2/3 mRNA as well as GALR2/3 peptide production were lower in the ovary of PCOS rats. In summary, while our results did not show differences in plasma SPX levels, we observed tissue-dependent significant differences in the SPX/GALR2/3 levels between PCOS and control rats, what indicates possible new mechanisms of PCOS neuroendocrinology.

Mutation of spexin2 promotes feeding, somatic growth, adiposity, and insulin resistance in zebrafish.

Spexin2 (spx2) is a newly identified gene in vertebrates, but its biological functions remain unclear. In this study, we cloned the full-length cDNA of spx2 in zebrafish. The 288-bp open reading frame encodes a protein of 95 amino acids that contains a 14 amino acids mature peptide. Spx2 is highly expressed in brain and testis. Its expression was significantly downregulated in the hypothalamus after feeding treatment and 7 days of food deprivation. Using a zebrafish spx2-/- mutant line, we observed a greater amount of food intake and changes in mRNA levels of feeding factors. We found that, SPX2 acts as a satiety factor that inhibits food intake by downregulating the expression of agouti-related neuropeptide (agrp). Moreover, spx2 mutant fish exhibited a larger body size, excessive lipid accumulation, and insulin resistance. Taken together, our results revealed that SPX2 functions as a satiety factor involved in energy metabolic regulation in zebrafish.

Spexin modulates molecular thermogenic profile of adipose tissue and thermoregulatory behaviors in female C57BL/6 mice.

Thermoregulation is the physiological process by which an animal regulates body temperature in response to its environment. It is known that galanin, a neuropeptide widely distributed throughout the central nervous system and secreted by the gut, plays a role in thermoregulatory behaviors and metabolism. We tested the ability of the novel neuropeptide spexin, which shares sequence homology to galanin, to regulate these functions in female mice. Supraphysiological levels of spexin in C57BL/6 mice did not lead to weight loss after 50 days of treatment. Behavioral analysis of long-term spexin treatment showed it decreased anxiety and increased thermoregulatory nest building, which was not observed when mice were housed at thermoneutral temperatures. Treatment also disrupted the thermogenic profile of brown and white adipose tissue, decreasing mRNA expression of Ucp1 in BAT and immunodetection of ß3-adrenergic receptors in gWAT. Our results reveal novel functions for spexin as a modulator of thermoregulatory behaviors and adipose tissue metabolism.

Galanin peptide family regulation of glucose metabolism.

Recent preclinical and clinical studies have indicated that the galanin peptide family may regulate glucose metabolism and alleviate insulin resistance, which diminishes the probability of type 2 diabetes mellitus. The galanin was discovered in 1983 as a gut-derived peptide hormone. Subsequently, galanin peptide family was found to exert a series of metabolic effects, including the regulation of gut motility, body weight and glucose metabolism. The galanin peptide family in modulating glucose metabolism received recently increasing recognition because pharmacological activiation of galanin signaling might be of therapeutic value to improve insuin resistance and type 2 diabetes mellitus. To date, however, few papers have summarized the role of the galanin peptide family in modulating glucose metabolism and insulin resistance. In this review we summarize the metabolic effect of galanin peptide family and highlight its glucoregulatory action and discuss the pharmacological value of galanin pathway activiation for the treatment of glucose intolerance and type 2 diabetes mellitus.

The effect of umbilical cord blood spexin, free 25(OH) vitamin D3 and adipocytokine levels on intrauterine growth and anthropometric measurements in newborns.

Spexin is a newly described peptide and is known to reduce the uptake of long-chain fatty acids into adipocytes. The serum spexin levels of obese children between the ages of 12-18 are lower. The effect of serum spexin and free 25(OH) vitamin D3 levels on intrauterine development in newborns is unknown. Our aims is to evaluate the effects of spexin and adipocytokin levels in the cord blood of term newborn babies on the weight of the baby according to the gestation age (GA) and anthropometric measurement results. Babies who were born in our hospital and whose GA was ≥37 weeks were evaluated in three groups as appropriate for GA (AGA), small for GA (SGA) and large for GA (LGA). A total of 84 babies, including an equal number of infants in AGA, SGA and LGA groups, were included in the study. Spexin, leptin, active ghrelin, free 25(OH) vitamin D3, glucose, and insulin levels in the cord blood of infants were examined at birth. The results were compared according to GA and birth weight (BW). There was no statistically significant difference between groups in terms of mean spexin, active ghrelin, free 25(OH) vitamin D3, and insulin levels. The mean leptin level was significantly higher in LGA group than SGA and AGA groups (p 0.004). The mean spexin and leptin levels were higher in girls than in boys (respectively p value 0.029, 0.003). Although there is a significant positive correlation between BW, head circumference, height, umbilical circumference, umbilical circumference/height ratio and the mean leptin levels (p < 0.001), there was no significant correlation between mean spexin, active ghrelin, free 25 (OH) vitamin D3, insulin, and glucose levels. This study suggests that spexin may not have an effect on intrauterine development.

Longitudinal study on novel neuropeptides phoenixin, spexin and kisspeptin in adolescent inpatients with anorexia nervosa - association with psychiatric symptoms.

OBJECTIVES: It is hypothesized that novel neuropeptides such as phoenixin (PNX), spexin (SPX), and kisspeptin (KISS) are involved in the pathogenesis of eating disorders. The study presented here analyzed neuropeptide concentrations during the course of anorexia nervosa (AN) and aimed to correlate those values with anthropometric and psychometric measurements. METHODS: A longitudinal study was carried outin 30 AN adolescent patients and 15 age-matched healthy female controls. Selected neuroprotein serum levels were analyzed in malnourished patients (accAN) and following partial weight recovery (norAN), and these values were compared with the control group. RESULTS: In accAN patients, decreased serum PNX levels were detected while SPX serum concentrations were lower in the accAN and norAN patients. No differences were observed in KISS concentrations in all studied groups. CONCLUSIONS: In malnourished adolescent inpatients with AN, serum PNX and SPX level were decreased. The partial weight recovery normalized PNX concentrations but failed to normalize SPX levels. Therefore these two neuropeptides might be crucial for the etiology and course of the AN. The KISS levels did not change in the course of AN. The PNX levels were associated with some symptoms of eating disorders which may indicate its potential contribution in the regulation of emotions and behaviors in AN.

Changes in metabolic and hormonal profiles during transition period in dairy cattle - the role of spexin.

BACKGROUND: This study aimed to evaluate spexin as a novel blood marker and to describe the relationship of this peptide with selected biochemical metabolites measured during the transition period in dairy cows. Additionally, mRNA expression of the spexin gene as well as spexin receptors - galanin receptor type 2 and galanin receptor type 3, was investigated in several bovine tissues. Blood samples were collected at weekly intervals starting at 21 days before the estimated parturition day until 21 days in milk to determine concentrations of spexin, nonesterified fatty acids, ß-hydroxybutyrate acid, total and active ghrelin, progesterone, glucose, insulin, IGF-I, triglycerides, cholesterol, leptin, corticosterone and 17-ß-estradiol as well as the activity of aspartate transaminase, alkaline phosphatase and gamma-glutamyl transferase. RESULTS: Spexin concentration decreased from 21 d before parturition to calving day and next it rose during the first 14 d of lactation. The lowest concentration of spexin was recorded on the calving day and it differed from the mean level of this peptide before parturition as well as postpartum. Moreover, differences were observed between mean spexin concentrations before and after calving. Spexin levels were moderately negatively correlated with NEFA (r = - 0.39) and total ghrelin contents (r = - 0.41), weakly correlated with BHBA (r = - 0.35) while they showed a moderate positive relationship with progesterone concentrations (r = 0.42). Moreover, we detected that mRNA expression of GALR2, GALR3 and SPX is present in various bovine tissues (kidney, bowel, rumen, spinal cord, lung, skeletal muscle, liver, heart, fat and spleen). CONCLUSION: A negative correlation between spexin concentration and NEFA, BHBA and total ghrelin contents as well as a positive relationship with levels of progesterone, metabolites and hormones, which are key players in the dairy cow transition period, may confirm an important function of this peptide in metabolism regulation. Thus measurement of spexin concentration could provide useful supplementary information for dairy cow herd health monitoring.

Short-term changes and correlations of plasma spexin, kisspeptin, and galanin levels after laparoscopic sleeve gastrectomy.

PURPOSE: To determine the circulating levels of spexin, kisspeptin, galanin, and the correlations between these peptides after laparoscopic sleeve gastrectomy (LSG). METHODS: The plasma levels of the spexin, kisspeptin, and galanin and metabolic parameters (body mass index, weight loss, % excess weight loss, body fat, fasting glucose, HbA1C, and cholesterol levels) were measured (baseline, 1 month, and 3 months) and correlated in thirty adult individuals with obesity (22 female and 8 male) after LSG. RESULTS: The body mass index (BMI), body fat, fasting glucose, total and low-density lipoprotein cholesterol decreased, while high-density lipoprotein cholesterol and % EWL (excess weight loss) increased at 3 months after surgery. The plasma spexin levels increased at 3 months, kisspeptin levels increased at 1 month and stabilized afterward, and galanin levels decreased at 3 months after LSG. Significant correlations were found between metabolic parameters with spexin, kisspeptin, and galanin. In addition, spexin and kisspeptin were negatively correlated with galanin, while spexin was positively correlated with kisspeptin. CONCLUSIONS: The biochemical data reveal evidence that LSG causes an increase in the levels of spexin, and kisspeptin and a decrease in galanin levels. Our findings, therefore, suggest a possible interaction between these novel peptides, which have potential roles in obesity and glucose metabolism.

Adropin and spexin hormones regulate the systemic inflammation in adenine-induced chronic kidney failure in rat.

Chronic kidney disease is one of the major global health problems. Chronic renal failure is stimulated by many cytokines and chemokines. Adropin and spexin (SPX) are peptides hormones. These peptides could affect inflammatory conditions, but this is unclear. Due to the limited information, we planned to investigate the impact of adropin and SPX hormones on systemic inflammation in adenine induced chronic kidney failure rat model. Chronic kidney failure was induced by administering adenine hemisulfate. Renal functions were measured by an autoanalyzer. Granulocyte colony-stimulating factor (G-CSF), interferon-gamma (IFN-γ), interleukin (IL)-1ß, IL-2, IL-4, IL-5, IL-10, IL-12, IL-13, IL-17A, tumor necrosis factor-alpha, Eotaxin, growth-regulated oncogene-alpha, IP-10, monocyte chemoattractant protein (MCP)-1, MCP-3, macrophage inflammatory protein (MIP)-1α, MIP-2, and RANTES levels were determined by Luminex. We observed an increase in 24-h urine volume and serum creatinine. Blood urea nitrogen (BUN) and urine protein levels were also significantly higher in the chronic kidney failure (CKF) group. Urine protein and 24-h urine volume were reduced with adropin and SPX treatments. Furthermore, G-CSF, IFN-γ, IL-4, IL-5, IL-10, IL-12, IL-17A, and GRO-α significantly increased by CKF induction; however, these cytokines and chemokines significantly decreased by adropin treatment in the CKF group. Furthermore, adropin increased IP-10, MCP-1, MIP-1α, and MIP-2 levels. In addition, SPX treatment had a more limited effect, decreasing only G-CSF, IFN-γ, and IL-5 levels. The combined adropin + SPX treatment significantly reduced G-CSF, IFN-γ, IL-4, IL-5, IL-12, and IL-17A. Furthermore, IP-10, MCP-1, MCP-3, and MIP-2 were significantly increased by these combined treatments. Our findings indicate that renal functions and inflammatory response were modulated by adropin and SPX peptides. These peptides may have protective effects on systemic inflammation and renal failure progression.

Neuropeptidergic Control of Feeding: Focus on the Galanin Family of Peptides.

Obesity/overweight are important health problems due to metabolic complications. Dysregulation of peptides exerting orexigenic/anorexigenic effects must be investigated in-depth to understand the mechanisms involved in feeding behaviour. One of the most important and studied orexigenic peptides is galanin (GAL). The aim of this review is to update the mechanisms of action and physiological roles played by the GAL family of peptides (GAL, GAL-like peptide, GAL message-associated peptide, alarin) in the control of food intake and to review the involvement of these peptides in metabolic diseases and food intake disorders in experimental animal models and humans. The interaction between GAL and NPY in feeding and energy metabolism, the relationships between GAL and other substances involved in food intake mechanisms, the potential pharmacological strategies to treat food intake disorders and obesity and the possible clinical applications will be mentioned and discussed. Some research lines are suggested to be developed in the future, such as studies focused on GAL receptor/neuropeptide Y Y1 receptor interactions in hypothalamic and extra-hypothalamic nuclei and sexual differences regarding the expression of GAL in feeding behaviour. It is also important to study the possible GAL resistance in obese individuals to better understand the molecular mechanisms by which GAL regulates insulin/glucose metabolism. GAL does not exert a pivotal role in weight regulation and food intake, but this role is crucial in fat intake and also exerts an important action by regulating the activity of other key compounds under conditions of stress/altered diet.

Decreased levels of spexin are associated with hormonal and metabolic disturbance in subjects with polycystic ovary syndrome.

Spexin, a newly identified peptide hormone, is involved in energy metabolism and the hypothalamic gonadal axis. We aimed to compare the altered levels of spexin in women with and without polycystic ovary syndrome (PCOS) and to find out if there was any association between spexin levels and hormonal-metabolic parameters in women with PCOS. Eighty subjects with PCOS and 80 age- and body mass index (BMI)-matched subjects with a normal menstrual cycle were enrolled into the current case control study. Spexin levels were measured by ELISA. Spexin levels were significantly lower in PCOS subjects. Spexin showed a negative correlation with insulin resistance, BMI and androgens in PCOS women. Binary logistic regression analysis showed that the risk of having PCOS was associated with low levels of spexin. Decreased spexin levels were inversely associated with androgens and unfavourable metabolic profiles in PCOS subjects, suggesting that the inter-related roles of spexin are in the different metabolic and hormonal pathways of PCOS.IMPACT STATEMENTWhat is already known on this subjects? Spexin is a newly identified peptide hormone which plays various roles in regulating energy metabolism and the hypothalamic gonadal axis. PCOS is a reproductive and metabolic disorder associated with insulin resistance and hypothalamic-pituitary-gonadal axis disruptions.What do the results of this study add? Decreased levels of spexin were inversely association with androgens and unfavourable metabolic profiles in PCOS women. The risk of having PCOS was increased in parallel with decreased spexin levels.What are the implications of these findings for clinical practice and/or further research? Spexin may play numerous roles in the pathophysiological processes of PCOS. To find the exact role of spexin over PCOS development, detailed investigations are required.

Different spexin level in obese vs normal weight children and its relationship with obesity related risk factors.

BACKGROUND AND AIMS: Spexin (SPX) is a novel peptide recently discovered as an important regulatory adipokine in obesity and related metabolic diseases. The aim of the current study was to determine the potential role of Circulating levels of SPX in obese children and explore its relationships with obesity-related risk factors, and its potential role in preventing obesity. METHODS AND RESULTS: Forty-five obese children and 45 normal-weight children of similar age and sex, with mean age of 13.73 (2.68) were recruited in this Study. Weight and height, blood pressure, resting metabolic rate (RMR), physical activity level, stress, anxiety and depression, appetite status, daily energy intake, pubertal stage, serum Spexin, Interleukin-10 (IL-10), IL-1ß, high-sensitivity C-reactive protein (hs-CRP), fasting glucose, insulin and lipid profile, were measure during standard techniques. Median (IQR) of Spexin levels were significantly lower in obese vs. normal-weight children [120.70 (77.7) pg/mL vs.145 (186.7)pg/mL; P = 0.03]. Based on the tertiles of the serum Spexin levels, a protective independent effect was observed for the highest tertile of serum Spexin concentrations. Crude OR (CI): 0.33 (0.11-0.95), P-trend = 0.04. Model 1 OR (CI): 0.20 (0.05-0.73), P- trend = 0.01, Model 2 OR (CI): 0.22 (0.05-0.86), P -trend = 0.03. Serum Spexin concentration was significantly associated with IL-10, IL-1ß, fasting Insulin and HOMA-IR (P < 0.05). CONCLUSION: The lower circulating levels of Spexin in obese children compared to their normal-weight peers, the protective independent effect found for the highest tertile of serum Spexin, and its association with glucose metabolism and immune function observed in our study, suggest a potential role for this novel peptide in childhood obesity and its related metabolic disorders.