α-MSH Levels Research Articles

Comparison of orexigenic and anorexigenic neuropeptide levels in hyperemesis gravidarum patients with normal pregnant women: A prospective cohort study.

The aim of this study was to determine whether orexigenic neuropeptides, orexin and galanin, and anorexigenic neuropeptides, alpha-melanocyte-stimulating hormone (α-MSH) and cocaine- and amphetamine-regulated transcript (CART), are implicated in hyperemesis gravidarum (HG). Fifty pregnant women who had been diagnosed with HG between April 2022 and February 2023 at the Siirt University Faculty of Medicine Training and Research Hospital (tertiary center) were recruited for this study. An equal number of pregnant women without an HG diagnosis were included in the study as the control group. Participants' age, pregnancy history, medical history, thyroid function test results, complete blood count results, and electrolyte levels were recorded, and their orexin, galanin, α-MSH, and CART serum levels were analyzed using an enzyme-linked immunosorbent assay. No statistically significant differences in orexigenic neuropeptides (orexin and galanin) were observed between the HG and control groups. A statistical difference was found between an anorexigenic neuropeptide (α-MSH) and the control group (P = .012). Based on a receiver operating characteristic analysis, the α-MSH parameter was statistically significant for distinguishing between participants with an HG diagnosis and those without, with a sensitivity of 63.6%, specificity of 65.9%, and cutoff value of 11769.3 pg/mL (P = .012, area under curve: 0.655). Based on the severity classification of ketonuria (ketonuria levels of +1 or +2 were classified as mild, whereas levels of +3 or +4 were classified as moderate to severe), the anorexigenic CART neuropeptide was found to be a statistically significant diagnostic indicator of severe ketonuria (P = .020). α-MSH and CART levels were found to be related in HG patients and in HG patients with severe ketonuria.

Specific Salivary Neuropeptides Shift Synchronously during Acute Stress in Fire Recruits.

Once thought of as an immune-privileged site, we now know that the nervous system communicates in a bidirectional manner with the immune system via the neuroimmune axis. Neuropeptides constitute a component of this axis, playing critical roles in the brain and periphery. The function of salivary neuropeptides in the acute stress response is not well understood. The purpose of this study is to investigate salivary neuropeptide levels during acute stress. Salivary samples were collected from fire recruits engaged in a stress training exercise previously shown to induce acute stress, at three separate timepoints during the exercise and levels of oxytocin, neurotensin, Substance P, α-MSH, and β-Endorphin were measured using the Human Neuropeptide 5-Plex Custom Assay Eve Technologies. All neuropeptides increased throughout the acute stress simulation and during the recovery phase. Exploratory factor analysis (EFA) identified one factor contributing to baseline values across five neuropeptides and Pairwise Pearson Correlation Coefficient analysis showed positive correlations >0.9 for almost all neuropeptide combinations at the pre-stress timepoint. Further analysis identified negative and positive correlations between past-life trauma and self-assessed hardiness, respectively. Calculated neuropeptide scores showed an overall positive correlation to self-assessed hardiness. Altogether, our results suggest that salivary neuropeptides increase synchronously during acute stress and higher levels correlate with an increase in self-assessed hardiness. Further study is required to determine if interventions designed to enhance neuropeptide activity can increase stress resilience, especially in high-stress occupations such as firefighting.

The Effect of Endurance Training with Garlic and Stevia Supplementation on AgRP and α-MSH in Brain Tissue of Obese Wistar Rats

Background: The aim of this study is to investigate the effect of endurance training with garlic and stevia supplementation on AgRP and α-MSH in the brain tissue of obese Wistar rats. Methods: 36 obese male Wistar rats fed with a high-fat diet (24 g fat, 24 g protein, and 41 g carbohydrate/100 g) were divided into six groups, including: 1) sham; 2) stevia supplementation; 3) garlic supplementation; 4) endurance training; 5) stevia supplementation plus endurance training, and 6) garlic supplementation plus endurance training. Moreover, 6 rats were included in the healthy control group to investigate the effects of obesity on the research variable. Training groups performed incremental endurance training for 15-50 minutes at a speed of 15-25 m/min, for eight weeks. Garlic and stevia supplements were added to the diet of the supplementation groups at a dose of 250 mg/kg. Results: Levels of AgRP in stevia supplementation group were significantly higher than endurance training (P=0.019) and endurance training plus stevia supplementation (P=0.018) groups. Levels of α-MSH in the garlic supplementation (P=0.001), endurance training (P=0.002), stevia supplementation plus endurance training (P=0.001), and garlic supplementation plus endurance training (P=0.001) groups were significantly higher than the sham group. In addition, in the endurance training plus stevia supplementation group, the levels were significantly higher than the stevia supplementation group (P=0.002). Conclusion: Endurance training plus garlic supplementation as well as endurance training plus stevia supplementation seem to play a synergistic role in appetite control protein; however, more studies on AgRP changes, following training and garlic and stevia supplementation are needed.

Triphenyltin induced darker body coloration by disrupting melanocortin system and pteridine metabolic pathway in a reef fish, Amphiprion ocellaris

Triphenyltin (TPT) is a typical persistent organic pollutant whose occurrence in coral reef ecosystems may threaten the survival of reef fishes. In this study, a brightly colored representative reef fish, Amphiprion ocellaris was used to explore the effects of TPT at environmental levels (1, 10, and 100 ng/L) on skin pigment synthesis. After the fish were exposed to TPT for 60 days, the skin became darker, owing to an increase in the relative area of black stripes, a decrease in orange color values while an increase in brown color values, and an increase in the number of melanocytes in the orange part of the skin tissues. To explore the mechanisms by which TPT induces darker body coloration, the enzymatic activity and gene expression levels of the members of melanocortin system that affect melanin synthesis were evaluated. Leptin levels and lepr expression were found to be increased after TPT exposure, which likely contributed to the increase found in pomc expression and α-melanocyte-stimulating hormone (α-MSH) levels. Then Tyr activity and mc1r, tyr, tyrp1, mitf, and dct were upregulated, ultimately increasing melanin levels. Importantly, RT-qPCR results were consistent with the transcriptome analysis of trends in lepr and pomc expression. Because the orange color values decreased, pterin levels and the pteridine metabolic pathway were also evaluated. The results showed that TPT induced BH4 levels and spr, xdh, and gch1 expression associated with pteridine synthesis decreased, ultimately decreasing the colored pterin content (sepiapterin). We conclude that TPT exposure interferes with the melanocortin system and pteridine metabolic pathway to increase melanin and decrease colored pterin levels, leading to darker body coloration in A. ocellaris. Given the importance of body coloration for the survival and reproduction of reef fishes, studies on the effects of pollutants (others alongside TPT) on body coloration are of high priority.

Immunopotentiating effects of herb-partitioned moxibustion on the spleens of cyclophosphamide-induced immunosuppressed rats

BackgroundTo investigate the effec of the herb-partitioned moxibustion on T-lymphocyte activity in immunosuppressed rats through differential modulation of the immune checkpoint molecules CD28 and CTLA-4.MethodsForty-eight Sprague‒Dawley rats were randomly divided into the normal group (NG), the cyclophosphamide model group (CTX), the herb-partitioned moxibustion group (HPM), the CD28 inhibitor + herb-partitioned moxibustion group (aCD28 + HPM), the CTLA-4 inhibitor + herb-partitioned moxibustion group (aCTLA-4 + HPM), and the levamisole group (LEV) (8 rats per group). The immunosuppression model was prepared using cyclophosphamide. HPM treatments was performed via herb-partitioned moxibustion at 4 acupoints, Zhongwan (CV12), Shenque (CV8), Guanyuan (CV4), and Zusanli (ST36). Subsequently, the moxa floss was made into a conical moxa cone, which was then placed on the herbal cake and ignited. Five consecutive moxibustion strokes were performed daily for 10 consecutive days. In addition to the same moxibustion, each rat in the aCD28 + HPM group was injected intraperitoneally with 0.5 mg/kg of CD28 inhibitor per rat on the first day of treatment, and 100 μL of CTLA-4 inhibitor was injected into the aCTLA-4 + HPM group on Days 1, 4, and 7. For the positive control, levamisole (LEV) was administered by gavage at a dose of 2 mg/kg once daily for 10 days.ResultsCompared with those in CTX model rats, the WBC counts in the HPM and other groups were significantly higher. The immobility time of EPM in the HPM group was significantly lower than that of the CTX group. The HE stainin results also showed that after treatment, the the marginal zone area of the spleen tissue in the HPM increased, the number of lymphatic sheath lymphocytes around the small central artery of the spleen increased, and the amount of red pulp containing a small amount of pigmentation was partially reduced. Compared with those in the CTX group, the serum levels of CD28, CTLA-4, B7-1, and B7-2 were significantly lower, and the levels of α-MSH, TrkB, and BDNF were significantly greater in the HPM group. The results of the flow cytometry assay showed a significant increase in the number of CD8 + T lymphocytes after treatment with HPM or other agents compared to that in the CTX group. The immunofluorescence results showed that the levels of CD28 and CTLA-4 lower in spleen tissues than in control tissues, and the binding ability of CD28 to B7-1 and B7-2 was weakened after treatment with HPM and other treatments compared with CTX rats, PCR for CD28, CTLA-4 and B7-1 showed similar results.ConclusionIn the immunosuppressive rat model induced by cyclophosphamide, HPM upregulated the expression of α-MSH, TrkB, and BDNF, and downregulated the expression of CD28 and CTLA-4, thereby enhancing the activity of CD8+ T lymphocytes, restoring spleen function, improving the immunosuppressive state, restoring immune function, and effectively alleviating depressive symptoms.

Alterations of serum neuropeptide levels and their relationship to cognitive impairment and psychopathology in male patients with chronic schizophrenia

Serum neuropeptide levels may be linked to schizophrenia (SCZ) pathogenesis. This study aims to examine the relation between five serum neuropeptide levels and the cognition of patients with treatment-resistant schizophrenia (TRS), chronic stable schizophrenia (CSS), and in healthy controls (HC). Three groups were assessed: 29 TRS and 48 CSS patients who were hospitalized in regional psychiatric hospitals, and 53 HC. After the above participants were enrolled, we examined the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and the blood serum levels of α-melanocyte stimulating hormone (α-MSH), β-endorphin (BE), neurotensin (NT), oxytocin (OT) and substance.P (S.P). Psychiatric symptoms in patients with SCZ were assessed with the Positive and Negative Syndrome Scale. SCZ patients performed worse than HC in total score and all subscales of the RBANS. The levels of the above five serum neuropeptides were significantly higher in SCZ than in HC. The levels of OT and S.P were significantly higher in CSS than in TRS patients. The α-MSH levels in TRS patients were significantly and negatively correlated with the language scores of RBANS. However, the BE and NT levels in CSS patients were significantly and positively correlated with the visuospatial/constructional scores of RBANS. Moreover, the interaction effect of NT and BE levels was positively associated with the visuospatial/constructional scores of RBANS. Therefore, abnormally increased serum neuropeptide levels may be associated with the physiology of SCZ, and may cause cognitive impairment and psychiatric symptoms, especially in patients with TRS.

SIRT7 Inhibits Melanin Synthesis of PIG1 and PIG3V by Suppressing the Succinylation of EZR.

Vitiligo is an autoimmune disease characterized by loss of skin pigmentation and currently has no effective treatment. This study aimed to investigate the function of SIRT7, being an important desuccinylase mediating multiple disease progression, and its mechanism in vitiligo progression. Normal human melanocytes (NHM) PIG1 and vitiligo human melanocytes (VHM) PIG3V were utilized in this research. The role of sirtuin 7 (SIRT7) and Ezrin (EZR) on melanin synthesis was investigated by detecting tyrosinase activity, melanin content, α-MSH levels, and the protein levels of melanin-related markers. The function of EZR was identified via rescue experiments, while the underlying mechanism was investigated via bioinformatic analysis, co-immunoprecipitation (co-IP), immunoprecipitation (IP), and Western blot techniques. Results showed that only SIRT7 was highly expressed in vitiligo human melanocytes, where knockingdown SIRT7 translated into increased melanin synthesis in melanocytes. Mechanistically, SIRT7 knockdown promoted the succinylation of EZR at the Lys (K)60 site. Moreover, overexpressing EZR induced higher melanin synthesis in melanocytes, while its knocking down exerted the opposite effect by inhibiting SIRT7 knockdown-induced melanin synthesis. SIRT7 inhibited melanin synthesis in melanocytes by suppressing the succinylation of EZR. These findings are envisaged to provide a novel theoretical basis for vitiligo treatment.

Relationship Between Appetite-Related Peptides and Frailty in Older Adults

ABSTRACT Background Frailty, is a geriatric syndrome that reduces the resistance to stress situations caused by activities of daily living and increases morbidity and mortality. We hypothesized that a decrease in orexigenic peptides or an increase in anorexigenic peptides might be associated with frailty. We aimed to investigate the relationship between frailty and six appetite-related peptides: ghrelin, neuropeptide Y (NPY), agouti-related peptide (AgRP), cocaine-amphetamine-associated peptide (CART), peptide YY, and alpha MSH (α-MSH). Methods This cross-sectional study was conducted on 85 older adults who visited the outpatient clinic. All patients underwent comprehensive geriatric assessment. Frailty status was assessed using the Fried frailty index. Plasma levels of six appetite-related peptides were studied. Results The mean age was 73.7 ± 5.4 years, 27 (31.8%) of the patients were male, and 32 of the patients (37.6%) were frail. While plasma levels of ghrelin, NPY and AgRP were significantly lower in frail patients, CART and α-MSH levels were higher compared to non-frail patients (p < .05 for all). Peptide YY was found to be higher in the frail group, however, the difference did not reach statistical significance (p = .052). In multivariate logistic regression analysis, the ghrelin, AgRP, CART, and α-MSH levels were independent predictors of frailty. Moreover, a weak correlation was found between all peptides(except NPY) and handgrip strength and Lawton-Brody score. Conclusion Ghrelin, AgRP, CART, and α-MSH levels were found to be independent predictors of frailty. Our results suggest that appetite-related peptides might be playing roles in the pathogenesis of frailty. Further larger prospective studies are needed to test this hypothesis.

The Effect of Background Color on Skin Color Variation of Juvenile Plectropomus leopardus.

Fish skin color is usually strongly affected by the background color of their environment. The study investigated the effects of five different background colors on the skin color of leopard coral groupers (Plectropomus leopardus). More than 450 juveniles were reared in Blue, Red, Black, White, and Transparent background tanks for 56 days. The paraffin section showed that the skin melanin zone of fish in the White group was smaller, whereas the Black and Red groups (especially Black) were nearly the largest. The apparent skin color of P. leopardus was red on the white background, which darkened in response to the other color backgrounds. The Black group revealed the blackest skin color, followed by the transparent group. Moreover, the White group had the highest L*, a*, and b* values. The melanin content and tyrosinase activity in the dorsal and ventral skin of the Black group were significantly higher than those in the other groups (p < 0.05), and the serum α-MSH level was higher in the Black group as well. The carotenoid and lutein contents showed completely different trends among the experimental groups, as carotenoid content was higher in the Red and White groups, while lutein content was higher in the Transparent group. The expression level of scarb1 was highest in the Blue and White groups, followed by the Transparent group, and lowest in the Black group (p < 0.05). The expression trend of scarb1 was similar to the skin color in different backgrounds, indicating that the background color regulated scarb1 expression level through visual center, then influenced the uptake and transport of carotenoids, then influenced the skin color formation of P. leopardus. Moreover, lighter colors inhibited the formation of melanocytes and had a significant effect on carotenoid and lutein contents. Pigment-related genes were involved in the regulation of fish skin color, and they were affected by background color in P. leopardus. These results indicate that a white background is more conducive to maintaining red skin color in juvenile P. leopardus.

Serum levels of hormones regulating appetite in patients with cystic fibrosis − a single-center, cross-sectional study

Cystic fibrosis (CF), which is the most common inherited genetically determined disease caused by a mutation in the gene for the CF transmembrane conductance regulator protein. Pulmonary failure is the leading cause of death in this population, while the dysregulation of endocrine system creates significant disorders, including malnutrition, underweight, and CF-related diabetes. Therefore, the objective of our study was to determine the following hormones in the serum of patients with CF: ghrelin, putative peptide YY (PYY), Agouti-signaling protein (ASP), and alpha-melanocyte-stimulating hormone (α-MSH). To our knowledge, serum levels of PYY, ASP, and α-MSH have not yet been assessed in CF. For this purpose, we measured hormone levels using enzyme-linked immunosorbent assays in 38 patients from the local CF care center, as well as 16 sex- and age-matched healthy controls. Moreover, we estimated the correlations between the tested hormones and the parameters of the patients’ clinical status. In this study, we found sinificantly reduced serum levels of ghrelin and ASP in patients with CF (p<0.01). There was no difference in PYY and α-MSH levels between participants with CF and healthy subjects. Furthermore, there was no difference in hormone levels between females and males with CF. The type of gene mutation (homozygous or heterozygous for ΔF508) had no effect on hormone levels. Ghrelin was negatively correlated with age, body mass index, and C-reactive protein. PYY was negatively associated with the age of the patients. Hormone dysregulation in CF may contribute to decreased appetite, as well as many other disturbed processes. Therefore, ghrelin appears to play a key role in the regulation of energy management of CF. Future multicenter and multidisciplinary studies should focus on an unequivocal understanding of the role of these hormones in CF.

Intestinal permeability and appetite regulating peptides-reactive immunoglobulins in severely malnourished women with anorexia nervosa

In the last decades, the role of microbiota-gut-brain axis has emerged in the regulation of eating behavior and in the pathophysiology of anorexia nervosa (AN) that remains poorly understood. Particularly, a gut-derived dysregulation of immune response has been proposed leading to immunoglobulins directed against appetite-regulating peptides. However, intestinal permeability in patients with anorexia nervosa has been poorly documented. In the present prospective case-control study, we thus compared intestinal permeability, appetite-regulating peptides and their reactive immunoglobulins measured in severely malnourished women with AN (n=17; 28 [21-35] y; 14.9 [14.1-15.2] kg/m2) to healthy volunteers (HV, n=34; 26 [23-35] y; 22.3 [20.6-23.6] kg/m2). Patients with AN exhibited an increased urinary lactulose/mannitol ratio, both in 0-5h (0.033 [0.013-0.116]) and 5-24h samples (0.115 [0.029-0.582]), when compared to HV (0.02 [0.008-0.045], p=0.0074 and 0.083 [0.019-0.290], p=0.0174, respectively), suggesting an increased intestinal permeability. Urinary excretion of sucralose and plasma zonulin were not different. The levels of plasma total ghrelin and desacyl-ghrelin were increased in patients with AN compared to HV, whereas plasma leptin concentration was decreased. In addition, αMSH remained unchanged compared to HV. Finally, we did not observe any modification of the levels of total or free αMSH, leptin or ghrelin-reactive immunoglobulin G and M, as well as for their affinity properties. Only, a weak decrease of the dissociation constant (kd) for acyl-ghrelin-reactive IgG was observed in patients with AN (p=0.0411). In conclusion, severely malnourished patients with AN show a higher intestinal permeability than HV without evidence of an effect on appetite regulating peptides-reactive immunoglobulins.

Bee Pollen and Probiotics May Alter Brain Neuropeptide Levels in a Rodent Model of Autism Spectrum Disorders.

Neuropeptides play a major role in maintaining normal brain development in children. Dysfunction of some specific neuropeptides can lead to autism spectrum disorders (ASD) in terms of social interaction and repetitive behavior, but the exact underlying etiological mechanisms are still not clear. In this study, we used an animal model of autism to investigate the role of bee pollen and probiotic in maintaining neuropeptide levels in the brain. We measured the Alpha-melanocyte-stimulating hormone (α-MSH), Beta-endorphin (β-End), neurotensin (NT), and substance P (SP) in brain homogenates of six studied groups of rats. Group I served as control, given only PBS for 30 days; Group II as an autistic model treated with 250 mg PPA/kg BW/day for 3 days after being given PBS for 27 days. Groups III-VI were denoted as intervention groups. G-III was treated with bee pollen (BP) 250 mg/kg body weight/day; G-IV with Lactobacillus paracaseii (LB) (109 CFU/mL) suspended in PBS; G-V with 0.2 g/kg body weight/day Protexin®, a mixture of probiotics (MPB); and G-VI was transplanted with stool from normal animals (FT) for 27 days prior to the induction of PPA neurotoxicity on the last 3 days of study (days 28–30). The obtained data were analyzed through the use of principal component analysis (PCA), discriminant analysis (DA), hierarchical clustering, and receiver operating characteristic (ROC) curves as excellent statistical tools in the field of biomarkers. The obtained data revealed that brain levels of the four measured neuropeptides were significantly reduced in PPA-treated animals compared to healthy control animals. Moreover, the findings demonstrate the ameliorative effects of bee pollen as a prebiotic and of the pure or mixed probiotics. This study proves the protective effects of pre and probiotics against the neurotoxic effects of PPA presented as impaired levels of α-MSH, β-End, NT, and SP.

Elevated Neuropeptides in Dry Eye Disease and Their Clinical Correlations.

The goal of this study was to assess neuropeptide levels in patients with dry eye disease (DED) and investigate their correlations with clinical characteristics. This study included 38 eyes of 38 patients diagnosed with DED (DED group) and 38 eyes of 38 healthy volunteers without DED (control group). Ocular surface evaluation was performed. The severity of dry eye symptoms and signs in the DED group was graded. Neuropeptides [substance P (SP), alpha-melanocyte-stimulating hormone (α-MSH), β-endorphin, neurotensin, and oxytocin] and inflammatory cytokines levels were measured in basal tears. The link between neuropeptides and clinical parameters was investigated using Spearman rank correlation. Overall, 76.3% of patients in the DED group showed dry eye symptoms and signs that were inconsistent in severity. Compared with the control group, the DED group showed higher levels of SP, α-MSH, and oxytocin in tears (P = 0.012, P = 0.030, and P = 0.006, respectively), but similar levels of β-endorphin and neurotensin (P = 0.269 and P = 0.052). The levels of SP, α-MSH, and oxytocin were elevated in DED patients with higher grading of symptoms than clinical signs (all P < 0.05). SP, α-MSH, and oxytocin levels in tears were positively correlated with Ocular Surface Disease Index scores, frequency of sensitivity to light, and frequency of blurred vision (all P < 0.05). The increased tear levels of SP, α-MSH, and oxytocin may be linked to ocular discomfort in DED. Neuropeptides may play a key role in the development of DED, especially in DED patients with more severe symptoms than clinical signs.

Elongator regulates the melanocortin satiety pathway

This study investigates the function of Elp1 and Elongator in the pituitary gland. Two conditional knockout models were generated where Elp1 was selectively deleted in either somatotropes of the anterior pituitary or Pomc-expressing cells of the anterior and intermediate pituitary. Although loss of Elp1 in somatotropes did not significantly impact murine growth or development, its loss in Pomc-expressing cells resulted in dramatically reduced levels of α-MSH, hyperphagia and obesity. This report provides the first evidence that Elongator plays an essential role in regulating the melanocortin satiety pathway.

The G209R mutant mouse as a model for human PCSK1 polyendocrinopathy.

PCSK1 encodes an enzyme required for prohormone maturation into bioactive peptides. A striking number of SNPs and rare mutations in PCSK1 are associated with a range of clinical phenotypes. Infants bearing two copies of a catalytically inactivating mutation, such as G209R, exhibit life-threatening chronic diarrhea and subsequently develop systemic endocrinopathies. Using CRISPR/Cas9 technology, we have engineered a mouse model bearing a G209R missense mutation in exon 6 of the murine Pcsk1 locus. Most pups homozygous for the G209R mutation succumbed by day 2, and surviving pups were severely dwarfed. In homozygous (but not heterozygous) pups, blood glucose levels were significantly lower, accompanied by elevated plasma insulin-like immunoreactivity and accumulation of large quantities of unprocessed proinsulin in the pancreas. Peptide hormone processing was also aberrant in G209R mouse pituitary, with mature ACTH levels markedly reduced in homozygotes, accompanied by a significant accumulation of POMC. We also observed a significant reduction in PC1/3 protein in the brains of G209R homozygous mice by Western blotting, while PC2 levels remained unaffected. Most likely due to the continued presence of PC2, pituitary and brain levels of α-MSH were not impaired. Analysis of intestinal cell types indicated a modest reduction of enteroendocrine cells in G209R homozygotes. We suggest that the G209R Pcsk1 mouse model recapitulates many of the dramatic neonatal deficiencies of human patients with this homozygous mutation.

Association between Ag-RP, alpha-MSH and cardiovascular risk factors regarding adherence to diet quality index-international (DQI-I) among obese individuals.

Introduction: Obesity is a strong promoter of cardiometabolic risk factors and is associated with several chronic comorbidities. Recently, the role of α-melanocyte stimulating hormone (α-MSH) and agouti related peptide (Ag-RP) in regulation of energy balance has attracted much attention. In current study, we evaluated the association between α-MSH and Ag-RP with cardiometabolic factors among obese individuals with different adherence to Diet Quality Index-International (DQI-I) values. Methods: In this research, 188 obese adults aged between 20 and 50 years old and body mass index (BMI) between 30 and 40 kg/m2 were recruited. Dietary intakes of participants and DQI-I calculation was performed using a semi-quantitative food frequency questionnaire (FFQ) with 132 food items. Serum glucose, lipids, insulin, and plasma α-MSH and Ag-RP levels were measured using ELISA kits. Homeostasis model assessment for insulin resistance index (HOMA-IR) and quantitative insulin sensitivity check index (QUICKI) were also calculated. Results: Among those with the lowest adherence to DQI-I, Ag-RP was positively associated with systolic blood pressure (SBP) (P = 0.03) among males, which was associated with waist circumference (WC) (P = 0.01) and diastolic blood pressure (DBP) (P = 0.01). Moreover, among males with low and moderate adherence to DQI-I, α-MSH was positively associated with insulin (P = 0.04), weight (P = 0.03), WC (P < 0.01), SDP (P = 0.02) and DBP (P = 0.01). Also, Ag-RP showed a positive association with BMI values (R2 = 0.03; P = 0.03). Conclusion: According to our findings, in obese subjects with poor to moderate adherence to DQI-I, Ag-RP and α-MSH were in positive correlation with cardiometabolic risk factors. These findings further clarify the clinical importance of these parameters as prognostic factors of cardiometabolic abnormalities.

GW9508 ameliorates cognitive dysfunction via the external treatment of encephalopathy in Aβ1-42 induced mouse model of Alzheimer's disease

The functions and mechanisms of GPR40 receptor to ameliorating the Alzheimer's disease (AD) by external treatment of encephalopathy remain unknown. In present study, the typical Aβ1-42 induced mice model was applied to explore the functions and mechanisms of GPR40 receptor by external treatment of encephalopathy in AD. GPR40 agonist GW9508 and antagonist GW1100 were given by i.g injection to activate/inhibit the GPR40 receptor respectively in the gut of AD mouse which illustrated the function and mechanism of GPR40 receptor in ameliorating AD symptoms by external treatment of encephalopathy. A series of behavioral experiments were used to investigate the cognitive function and memory ability of mice, while molecular biology experiments such as Western blot, ELISA, flow cytometry were used to detect the corresponding changes of signaling pathways. The results revealed that intragastric administrated GW9508 could significantly ameliorate cognitive deficits of AD mouse, up-regulate the expression levels of gut-brain peptides both in blood circulation and hypothalamus thus up-regulate the expression levels of α-MSH in hypothalamus, while the negative autophagy-related proteins and inflammation-related proteins were down-regulated correspondingly. Meanwhile, GW9508 could also inhibit the pathological process of neuroinflammation in microglia. GW1100 reversed the effects of GW9508 significantly. These results suggested that GPR40 was an underlying therapeutic target for the external treatment of encephalopathy related to AD and GPR40 agonist could be explored as the emerging AD therapeutic drug.

Fototerapi Alfa Melanosit Uyarıcı Hormon Seviyelerini Etkiler mi?

Objective: We aimed to investigate the effect of phototherapy on plasma alpha-melanocyte-stimulating hormone (α-MSH) levels of newborns with indirect hyperbilirubinemia (IHB) for the first time. Materials and Methods: A total of 45 cases, who were hospitalized in neonatal intensive care units between July 1, 2019, to September 30, 2019, and received phototherapy, were retrospectively included in the study. Plasma α-MSH and bilirubin levels were measured before and after the phototherapy. Results: A total of 45 newborns (19 girls and 26 boys) were included in to study. The average birth weight was 3202 grams and the mean total bilirubin level was 17.2 mg/dL. α-MSH levels before and after phototherapy were 326.2 (4.0-2228.0) ng/L and 373.9 (8.7-2283.0) ng/L, respectively and did not represent a significant difference (p&amp;gt;0.05). Conclusion: This study demonstrated that there was no effect between phototherapy applied for newborn IHB and plasma α-MSH levels.

The in vitro and in vivo depigmenting activity of pterostilbene through induction of autophagy in melanocytes and inhibition of UVA-irradiated α-MSH in keratinocytes via Nrf2-mediated antioxidant pathways

Pterostilbene (Pt) is a natural polyphenol found in blueberries and several grape varieties. Pt's pharmacological importance was well documented. Nevertheless, the depigmenting effects are not demonstrated. We evaluated the Pt's depigmenting effects through autophagy induction in B16F10 cells and inhibition of UVA (3 J/cm2)-irradiated α-MSH in keratinocyte HaCaT cells via Nrf2-mediated antioxidant pathways. Pt (2.5–5μM) attenuated ROS production and downregulated the POMC/α-MSH pathway in HaCaT cells. The conditioned medium-derived from UVA-irradiated HaCaT pretreated with Pt suppressed melanogenesis in B16F10 through MITF-CREB-tyrosinase pathway downregulation. Interestingly, Pt-induced HaCaT autophagy was revealed by enhanced LC3-II accumulation, p62/SQSTM1 activation, and AVO formation. Pt significantly decreased melanosome gp100 but increased LC3-II levels in HaCaT cells exposed to B16F10-derived melanin. Pt activated and facilitated the Nrf2 antioxidant pathway in HaCaT cells leading to increased HO-1, γ-GCLC, and NQO-1 antioxidant protein expression. ERK, AMPK, and ROS pathways mediate the Nrf2 activation. However, Nrf2 knockdown suppressed Pt's antioxidant ability leading to uncontrolled ROS and α-MSH levels after UVA-irradiation suggested the essentiality of the Nrf2 pathway. Moreover, in α-MSH-stimulated B16F10 cells, Pt (10–30 μM) downregulated the MC1R, MITF, tyrosinase, TRP-1/-2, and melanin expression. Further, Pt showed potent anti-melanogenic effects through autophagy induction mechanism in B16F10 cells, verified by increased LC3-II/p62 levels, AVO formation, and Beclin-1/Bcl-2 ratio, decreased ATG4B levels and PI3K/AKT/mTOR pathway. Transmission electron microscopy provided direct evidence by showing autophagosomes engulfing melanosomes following Pt treatment in α-MSH-stimulated B16F10 cells. Moreover, Pt-induced anti-melanogenic activity through the downregulation of CREB-MITF pathway-mediated TRP-1/-2, tyrosinase expressions, melanosome formation, and melanin synthesis was substantially reversed due to 3-MA (autophagy inhibitor) pretreatment or LC3 silencing in B16F10 cells. In vivo results also confirmed that Pt-inhibited tyrosinase expression/activity and endogenous pigmentation in the zebrafish model. Therefore, pterostilbene is a potent skin-whitening and antioxidant agent and could be used in skin-whitening formulations as a topical applicant.

Correlation between serum α-MSH and vitamin D levels in vitiligo patients

Background: Vitiligo is a skin disease caused by the destruction of melanocytes of the epidermis, leading to well-defined white patches that are often distributed symmetrically. The presentstudy aimed to determine the correlation relationship between the α-MSH and vitamin D serum levels among Iraqi vitiligo patients. Materials and Methods: This study was done on outpatients who attended the Dermatology and Venereology Consulting Clinic of Salah-Al Deen General Hospital from November 2017 to March 2018. One hundred and ninety individuals were stratified into 110 cases of vitiligo and 80 healthy controls. Serum assays for α-MSH and vitamin D levels were sent for all subjects. Results: Vitiligo patients had significantly lower α-MSH levels and vitamin D levels than the controls (P ≤ 0.01). There was a significant, positive correlation between α-MSH and vitamin D levels in vitiligo patients overall (r = 0.236; P ≤ 0.01), though this correlation was negative within the male and female subgroups (r = -0.392 and -0.661, respectively; P ≤ 0.01). Conclusion: Compared to normal controls, vitiligo patients had significantly lower levels of α-MSH and vitamin D. These findings may back the normalization of both α-MSH and vitamin D levels in vitiligo patients as an important step toward disease recovery.