RESUMEN

OBJECTIVE: We aimed to investigate the serum concentration of the spexin, which has been shown to have an anorexic effect in animal models, in pregnant women with hyperemesis gravidarum (HG). METHODS: This case-control study was conducted with 80 pregnant women who applied to the Umraniye Training and Research Hospital Gynecology and Obstetrics Clinic between April 2022 and September 2022. The HG group consisted of 40 pregnant women who were diagnosed with HG in the first 14 weeks of pregnancy, and the control group consisted of 40 healthy pregnant women matched with the HG group in terms of age, BMI, and gestational week. RESULTS: Both groups were similar in terms of demographic characteristics and gestational age at blood sampling for spexin (p > 0.05). While maternal serum spexin concentration was 342.4 pg/ml in the HG group, it was 272.8 pg/ml in the control group (p = 0.003). ROC analysis was performed to determine the value of maternal serum spexin concentration in terms of predicting HG. AUC analysis of maternal serum spexin for HG estimation was 0.693 (p = 0.003, 95% CI =0.577 - 0.809). The optimal cutoff value for maternal serum spexin concentration was determined as 305.90 pg/ml with 65% sensitivity and 65% specificity. CONCLUSIONS: High serum spexin concentration is thought to play a role in the etiopathogenesis of HG, and this should be supported by demonstrating changes in serum spexin concentrations in pregnant women with HG whose symptoms alleviated and weight regain started after treatment.

Asunto(s)

Hiperemesis Gravídica , Hormonas Peptídicas , Humanos , Femenino , Embarazo , Hiperemesis Gravídica/sangre , Hiperemesis Gravídica/diagnóstico , Adulto , Estudios de Casos y Controles , Hormonas Peptídicas/sangre , Biomarcadores/sangre , Curva ROC , Adulto Joven

RESUMEN

Acute kidney injury (AKI) has emerged as a global health crisis, surpassing mortality rates associated with several cancers and heart failure. The lack of effective therapies, coupled with challenges in diagnosis and the high cost of kidney transplantation, underscores the urgent need to explore novel therapeutic targets and strategies for AKI. Understanding the intricate pathophysiology of AKI is paramount in this endeavor. The components of the apelinergic system-namely, apelin and elabela/toddler, along with their receptor-are prominently expressed in various kidney cells and have garnered significant attention in renal research. Recent studies have highlighted the renoprotective role of the apelinergic system in AKI. This system exerts its protective effects by modulating several pathophysiological processes, including reducing endoplasmic reticulum (ER) stress, improving mitochondrial dynamics, inhibiting inflammation and apoptosis, promoting diuresis through vasodilation of renal vasculature, and counteracting the effects of reactive oxygen species (ROS). Despite these advancements, the precise involvement of the apelinergic system in the progression of AKI remains unclear. Furthermore, the therapeutic potential of apelin-13 in AKI is not fully understood. This review aims to elucidate the role of the apelinergic system in AKI and its interactions with key pathomechanisms involved in the progression of AKI. Additionally, we discuss the current clinical status of exogenous apelin-13 therapy, providing insights that will guide future research on apelin against AKI.

Asunto(s)

Lesión Renal Aguda , Apelina , Lesión Renal Aguda/metabolismo , Humanos , Apelina/metabolismo , Animales , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Hormonas Peptídicas/metabolismo , Apoptosis , Estrés del Retículo Endoplásmico , Especies Reactivas de Oxígeno/metabolismo , Receptores de Apelina/metabolismo , Riñón/metabolismo , Riñón/patología

RESUMEN

OBJECTIVE: Prediabetes mellitus, hypertension, and their frequent coexistence are risk factors for macrovascular and cardiovascular complications. In this study we aimed to determine the relationship between spexin levels and echocardiographic findings and hypertension in prediabetic patients. METHODS: This study included 118 adult patients diagnosed with prediabetes mellitus who presented to outpatient clinics between April 2021 and January 2022. The patients were grouped into prediabetic patients with hypertension (n = 58) and those without hypertension (n = 60). The hypertension group was further divided into dipper and non-dipper groups according to the 24-hour ambulatory blood pressure monitoring. Blood samples were collected from all patients and echocardiography was performed. Spexin levels were measured by ELISA. Serum spexin levels, echocardiographic and ambulatory blood pressure monitoring findings were compared between the groups. RESULTS: The hypertension and non-dipper groups had significantly lower spexin levels and higher left atrial volume index, E/Em index, and interventricular septum and posterior wall thicknesses. Spexin levels were negatively correlated with body mass index (r = -0.298, P < 0.001), nighttime systolic blood pressure (r = -0.264, P = 0.006), nighttime diastolic blood pressure (r =-.255, P = 0.005), left atrial volume index (r =-.238, P = 0.009), E/Em (r =-.214,P = 0.020), and low-density lipoprotein cholesterol (r = -.243, P = 0.008). Obesity, overweight and spexin <780 pg/mL were independently associated with hypertension. CONCLUSION: Circulating spexin levels were lower in prediabetic patients with overall hypertension and in non-dipper patients, and were associated with echocardiographic and lipid parameters. The cut-off value of spexin identified in our study may be a useful indicator for hypertension detection and raise clinicians' awareness about evaluating prediabetic patients for hypertension.

Asunto(s)

Ecocardiografía , Hipertensión , Hormonas Peptídicas , Estado Prediabético , Humanos , Femenino , Estado Prediabético/sangre , Estado Prediabético/complicaciones , Estado Prediabético/diagnóstico por imagen , Hipertensión/sangre , Hipertensión/complicaciones , Masculino , Persona de Mediana Edad , Hormonas Peptídicas/sangre , Adulto , Monitoreo Ambulatorio de la Presión Arterial , Índice de Masa Corporal , Anciano

RESUMEN

This study aimed to assess the prevalence of thyroid dysfunction, as measured by hormone levels, in Saudi women with type 2 diabetes mellitus (T2DM). The study will also assess thyroid hormones and leptin, angiopoietin like 8 (ANGPTL8), obesity, and cardiovascular diseases (CVD) in T2D patients. A total of 250 women aged 40 to 60 years with T2DM were retrospectively studied between 2021 and 2022. This research examined medical records for T2DM patients. In this investigation, no T2DM patients had thyroid autoantibodies in their medical records. These patients were chosen for their FT4 and TSH values. All participants were Saudi females with T2DM, aged 54.5 years. Of the 250 participants, 32% had hypothyroidism, 14.8% had hyperthyroidism, and 40.8% (102) had no thyroid disease. Hypothyroidism (7.8 ±â€…0.67 mmol/L) exhibited greater fasting blood glucose (FBG) levels than hyperthyroidism (7.1 ±â€…0.64 mmol/L) (P < .05). Hypothyroid and hyperthyroid females had significant differences in high density lipoprotein-cholestrol (HDL-C), triglycerides, triglyceride glucose (TyG) index, body mass index (BMI), waist circumstance (WC), high-sensitivity C-reactive protein (hs-CRP), leptin, ANGPTL8, insulin resistance (IR), and insulin levels (P < .05). Pearson's correlation test showed that T2DM patients' HDL-C levels were favorably but negatively correlated with leptin and ANGPTL8 levels. In hypothyroidism, thyroid stimulation hormone (TSH) is favorably linked with glycated hemoglobin (HbA1c), triglyscride (TG), TyG index, BMI, WC, leptin, ANGPTL8, hs-CRP, and IR. T2DM is linked to thyroid malfunction, notably hypothyroidism, which correlates positively with TSH. TSH variations due to increasing leptin, ANGPTL8, and TyG index may enhance the risk of insulin resistance diseases, such as obesity and CVD, in Saudi females with T2DM.

Asunto(s)

Proteína 8 Similar a la Angiopoyetina , Proteínas Similares a la Angiopoyetina , Diabetes Mellitus Tipo 2 , Hipotiroidismo , Leptina , Hormonas Tiroideas , Humanos , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/epidemiología , Femenino , Leptina/sangre , Persona de Mediana Edad , Estudios Retrospectivos , Arabia Saudita/epidemiología , Adulto , Proteínas Similares a la Angiopoyetina/sangre , Hormonas Tiroideas/sangre , Hipotiroidismo/sangre , Hipotiroidismo/epidemiología , Hipertiroidismo/sangre , Hipertiroidismo/epidemiología , Índice de Masa Corporal , Glucemia/análisis , Glucemia/metabolismo , Obesidad/sangre , Obesidad/epidemiología , Tirotropina/sangre , Hormonas Peptídicas

RESUMEN

We investigated the effects of tobacco smoke exposure and abnormal body weight on selected peptide hormones and their association with metabolic and hormonal disorders in women with polycystic ovary syndrome (PCOS). The study group included 88 women with PCOS and 28 women without the disease. In women with PCOS, chemerin, lipocalin, and apelin concentrations were influenced by overweight and obesity status, with the highest concentrations observed in those with a body mass index (BMI) ≥ 30.0. Exposure to tobacco smoke significantly increased only lipocalin-2 concentration. The disease itself did not affect the concentrations of chemerin, lipocalin, and apelin. Additionally, we found a positive correlation between chemerin concentration and fasting glucose, fasting insulin, and triglycerides levels, while a negative correlation was observed with high-density lipoprotein (HDL-C) concentration. In the smoking subgroup, chemerin concentration was positively correlated with free testosterone concentration and the free androgen index and negatively associated with sex hormone-binding globulin concentration. Our findings indicate that abnormal body weight has a stronger impact than tobacco smoke exposure on metabolic and hormonal disorders in women with PCOS, highlighting the important role of weight control in such individuals. However, smoking appears to be an additional factor that intensifies hormonal disorders associated with adipose tissue.

Asunto(s)

Quimiocinas , Obesidad , Hormonas Peptídicas , Síndrome del Ovario Poliquístico , Fumar , Humanos , Femenino , Síndrome del Ovario Poliquístico/sangre , Síndrome del Ovario Poliquístico/metabolismo , Obesidad/sangre , Obesidad/metabolismo , Adulto , Hormonas Peptídicas/sangre , Quimiocinas/sangre , Fumar/efectos adversos , Fumar/sangre , Índice de Masa Corporal , Péptidos y Proteínas de Señalización Intercelular/sangre , Lipocalina 2/sangre , Apelina/sangre , Adulto Joven , Testosterona/sangre , Insulina/sangre

RESUMEN

Fuel substrate switching between carbohydrates and fat is essential for maintaining metabolic homeostasis. During aerobic exercise, the predominant energy source gradually shifts from carbohydrates to fat. While it is well known that exercise mobilizes fat storage from adipose tissues, it remains largely obscure how circulating lipids are distributed tissue-specifically according to distinct energy requirements. Here, we demonstrate that aerobic exercise is linked to nutrient availability to regulate tissue-specific activities of lipoprotein lipase (LPL), the key enzyme catabolizing circulating triglyceride (TG) for tissue uptake, through the differential actions of angiopoietin-like (ANGPTL) proteins. Exercise reduced the tissue binding of ANGPTL3 protein, increasing LPL activity and TG uptake in the heart and skeletal muscle in the postprandial state specifically. Mechanistically, exercise suppressed insulin secretion, attenuating hepatic Angptl8 transcription through the PI3K/mTOR/CEBPα pathway, which is imperative for the tissue binding of its partner ANGPTL3. Constitutive expression of ANGPTL8 hampered lipid utilization and resulted in cardiac dysfunction in response to exercise. Conversely, exercise promoted the expression of ANGPTL4 in white adipose tissues, overriding the regulatory actions of ANGPTL8/ANGPTL3 in suppressing adipose LPL activity, thereby diverting circulating TG away from storage. Collectively, our findings show an overlooked bifurcated ANGPTL-LPL network that orchestrates fuel switching in response to aerobic exercise.

Asunto(s)

Proteína 3 Similar a la Angiopoyetina , Proteína 8 Similar a la Angiopoyetina , Proteínas Similares a la Angiopoyetina , Lipoproteína Lipasa , Músculo Esquelético , Periodo Posprandial , Triglicéridos , Proteínas Similares a la Angiopoyetina/metabolismo , Proteínas Similares a la Angiopoyetina/genética , Triglicéridos/metabolismo , Animales , Ratones , Lipoproteína Lipasa/metabolismo , Músculo Esquelético/metabolismo , Proteína 3 Similar a la Angiopoyetina/metabolismo , Masculino , Humanos , Condicionamiento Físico Animal/fisiología , Proteína 4 Similar a la Angiopoyetina/metabolismo , Proteína 4 Similar a la Angiopoyetina/genética , Hormonas Peptídicas/metabolismo , Miocardio/metabolismo , Ejercicio Físico/fisiología , Hígado/metabolismo , Ratones Endogámicos C57BL , Metabolismo de los Lípidos

RESUMEN

BACKGROUND: Type 2 diabetes mellitus (T2D) is associated with an increased risk of cognitive dysfunction. Angiopoietin-like protein 8 (ANGPTL8) is an important regulator in T2D, but the role of ANGPTL8 in diabetes-associated cognitive dysfunction remains unknown. Here, we explored the role of ANGPTL8 in diabetes-associated cognitive dysfunction through its interaction with paired immunoglobulin-like receptor B (PirB) in the central nervous system. METHODS: The levels of ANGPTL8 in type 2 diabetic patients with cognitive dysfunction and control individuals were measured. Mouse models of diabetes-associated cognitive dysfunction were constructed to investigate the role of ANGPTL8 in cognitive function. The cognitive function of the mice was assessed by the Barnes Maze test and the novel object recognition test, and levels of ANGPTL8, synaptic and axonal markers, and pro-inflammatory cytokines were measured. Primary neurons and microglia were treated with recombinant ANGPTL8 protein (rA8), and subsequent changes were examined. In addition, the changes induced by ANGPTL8 were validated after blocking PirB and its downstream pathways. Finally, mice with central nervous system-specific knockout of Angptl8 and PirB-/- mice were generated, and relevant in vivo experiments were performed. RESULTS: Here, we demonstrated that in the diabetic brain, ANGPTL8 was secreted by neurons into the hippocampus, resulting in neuroinflammation and impairment of synaptic plasticity. Moreover, neuron-specific Angptl8 knockout prevented diabetes-associated cognitive dysfunction and neuroinflammation. Mechanistically, ANGPTL8 acted in parallel to neurons and microglia via its receptor PirB, manifesting as downregulation of synaptic and axonal markers in neurons and upregulation of proinflammatory cytokine expression in microglia. In vivo, PirB-/- mice exhibited resistance to ANGPTL8-induced neuroinflammation and synaptic damage. CONCLUSION: Taken together, our findings reveal the role of ANGPTL8 in the pathogenesis of diabetes-associated cognitive dysfunction and identify the ANGPTL8-PirB signaling pathway as a potential target for the management of this condition.

Asunto(s)

Proteína 8 Similar a la Angiopoyetina , Proteínas Similares a la Angiopoyetina , Disfunción Cognitiva , Diabetes Mellitus Tipo 2 , Ratones Noqueados , Receptores Inmunológicos , Transducción de Señal , Animales , Ratones , Disfunción Cognitiva/metabolismo , Disfunción Cognitiva/prevención & control , Disfunción Cognitiva/etiología , Transducción de Señal/fisiología , Transducción de Señal/efectos de los fármacos , Proteínas Similares a la Angiopoyetina/metabolismo , Proteínas Similares a la Angiopoyetina/genética , Humanos , Masculino , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/metabolismo , Receptores Inmunológicos/metabolismo , Receptores Inmunológicos/genética , Ratones Endogámicos C57BL , Sinapsis/metabolismo , Sinapsis/patología , Sinapsis/efectos de los fármacos , Hormonas Peptídicas/metabolismo , Persona de Mediana Edad , Femenino

RESUMEN

Spexin (SPX) is a 14-amino-acid peptide that plays an important role in the regulation of metabolism and energy homeostasis. It is well known that a variety of bioactive molecules released into the circulation by organs and tissues in response to acute and chronic exercise, known as exerkines, mediate the benefits of exercise by improving metabolic health. However, it is unclear whether acute exercise affects SPX levels in the circulation and peripheral tissues. This study aimed to determine whether acute treadmill exercise induces plasma SPX levels, as well as mRNA expression and immunostaining of SPX in skeletal muscle, adipose tissue, and liver. Male Sprague Dawley rats were divided into sedentary and acute exercise groups. Plasma, soleus (SOL), extensor digitorum longus (EDL), adipose tissue, and liver samples were collected at six time points (0, 1, 3, 6, 12, and 24 h) following 60 min of acute treadmill exercise at a speed of 25 m/min and 0 % grade. Acute exercise increased plasma SPX levels and induced mRNA expression of Spx in the SOL, EDL, and liver. Immunohistochemical analysis demonstrated that acute exercise led to a decrease in SPX immunostaining in the liver. Taken together, these findings suggest that SPX increases in response to acute exercise as a potential exerkine candidate, and the liver may be one of the sources of acute exercise-induced plasma SPX levels in rats. However, a comprehensive analysis is needed to fully elucidate the systemic response of SPX to acute exercise, as well as the tissue from which SPX is secreted.

Asunto(s)

Hígado , Músculo Esquelético , Hormonas Peptídicas , Condicionamiento Físico Animal , Ratas Sprague-Dawley , Animales , Masculino , Condicionamiento Físico Animal/fisiología , Músculo Esquelético/metabolismo , Ratas , Hígado/metabolismo , Hormonas Peptídicas/metabolismo , Hormonas Peptídicas/genética , Hormonas Peptídicas/sangre , Tejido Adiposo/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo

RESUMEN

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 latter two groups. High-fat diet together with streptozotocin (STZ) injection induced obesity and diabetes. The EX group underwent swimming, and the SPX group received SPX injections for 8 wk. Results showed significant improvements in thyroid function and 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.NEW & NOTEWORTHY This study proves, for the first time, the beneficial effects of SPX on thyroid dysfunction in obese diabetic rats and suggests that SPX mediates the EX effect on thyroid gland and exerts its effect mainly via GALR2.

Asunto(s)

Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Dieta Alta en Grasa , Obesidad , Hormonas Peptídicas , Condicionamiento Físico Animal , Glándula Tiroides , Animales , Ratas , Obesidad/metabolismo , Obesidad/terapia , Condicionamiento Físico Animal/fisiología , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/terapia , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/complicaciones , Diabetes Mellitus Experimental/terapia , Masculino , Hormonas Peptídicas/metabolismo , Glándula Tiroides/metabolismo , Glándula Tiroides/efectos de los fármacos , Ratas Wistar

RESUMEN

Liver injury is closely related to poor outcomes in sepsis patients. Current studies indicate that sepsis is accompanied by metabolic disorders, especially those related to lipid metabolism. It is highly important to explore the mechanism of abnormal liver lipid metabolism during sepsis. As a key regulator of glucose and lipid metabolism, angiopoietin-like 8 (ANGPTL8) is involved in the regulation of multiple chronic metabolic diseases. In the present study, severe liver lipid deposition and lipid peroxidation were observed in the early stages of lipopolysaccharide (LPS) induced liver injury. LPS promotes the expression of ANGPTL8 both in vivo and in vitro. Knockout of Angptl8 reduced hepatic lipid accumulation and lipid peroxidation, improved fatty acid oxidation and liver function, and increased the survival rate of septic mice by activating the PGC1α/PPARα pathway. We also found that the expression of ANGPTL8 induced by LPS depends on TNF-α, and that inhibiting the TNF-α pathway reduces LPS-induced hepatic lipid deposition and lipid peroxidation. However, knocking out Angptl8 improved the survival rate of septic mice better than inhibiting the TNF-α pathway. Taken together, the results of our study suggest that ANGPTL8 functions as a novel cytokine in LPS-induced liver injury by suppressing the PGC1α/PPARα signaling pathway. Therefore, targeting ANGPTL8 to improve liver lipid metabolism represents an attractive strategy for the management of sepsis patients.

Asunto(s)

Proteína 8 Similar a la Angiopoyetina , Proteínas Similares a la Angiopoyetina , Metabolismo de los Lípidos , Lipopolisacáridos , Animales , Ratones , Proteínas Similares a la Angiopoyetina/metabolismo , Proteínas Similares a la Angiopoyetina/deficiencia , Proteínas Similares a la Angiopoyetina/genética , PPAR alfa/metabolismo , PPAR alfa/genética , Masculino , Ratones Noqueados , Hormonas Peptídicas/metabolismo , Hígado/metabolismo , Hígado/patología , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/metabolismo , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/genética , Sepsis/metabolismo , Sepsis/inducido químicamente , Ratones Endogámicos C57BL , Factor de Necrosis Tumoral alfa/metabolismo , Peroxidación de Lípido/efectos de los fármacos , Transducción de Señal

RESUMEN

Hormones are specific molecules measured in biological fluids by elaborate analytical systems requiring meticulous attention. Variation between laboratories can be expected. However, recently published measurements of AVP, OXT, and BNP in human plasma under basal/control conditions include numbers which, between publications, vary by 100-10 000-fold. Generally, the methods descriptions are scant, at best, and provide no information about quality control measures. Clearly, two results describing the same basal hormone concentration by numbers three orders of magnitude apart are incongruent providing reason for concern. Basal concentrations of bioactive AVP, OXT, and BNP in human plasma are in the order of 1-10 pmol/L. Therefore, assay systems applied to plasma must be able to measure concentrations of less than 1 pmol/L with appropriate specificity and accuracy. Basal concentrations of AVP, OXT, and BNP above 100 pmol/L should be reconsidered, as such results do not reflect bioactive hormone levels in humans, rats, or mice. Any concentration above 1000 pmol/L is of concern because such levels of bioactive hormone may be seen only under extreme conditions, if at all.

Asunto(s)

Péptido Natriurético Encefálico , Oxitocina , Vasopresinas , Humanos , Oxitocina/sangre , Péptido Natriurético Encefálico/sangre , Vasopresinas/sangre , Animales , Hormonas Peptídicas/sangre

RESUMEN

BACKGROUND: Diabetic kidney disease (DKD) is one of the most serious microvascular complications of diabetes mellitus (DM) and the leading cause of chronic kidney disease (CKD) worldwide. Since obesity and type 2 DM (T2DM) are considered as inflammatory conditions, thus reducing their accompanied systemic inflammation may lessen their complications. Sestrin 2 belongs to a group of stress induced proteins which are produced in response to oxidative stress, inflammation and DNA damage. Betatrophin; a hormone that stimulates the growth, proliferation and mass expansion of pancreatic beta-cells and improves glucose tolerance. The objective of the study was to evaluate levels of serum Sestrin 2 and betatrophin in patients with different stages of diabetic nephropathy (DN)) and compare results with healthy control. METHODS: This cross sectional study was carried out on 60 patients above 18 years old, recruited from Tanta University hospitals out patients clinics and 20 apparently healthy individuals of matched sex and age as a control group. Participants were divided into two groups: group I: 20 normal subjects as control group and group II: 60 patients with type 2 DM,. further subdivided in to three equal groups: group 1IIA(20 patients) with normo-albuminuria (ACR < 30 mg/g), group IIB (20 patients) with micro albuminuria (ACR = 30 to 300 mg/g) and group IIC (20 patients) with macro albuminuria (ACR > 300 mg/g). They were subjected to detailed history taking, careful clinical examination and laboratory investigations including blood urea, serum creatinine, estimated glomerular filtration rate (eGFR), urinary albumin creatinine ratio, and specific laboratory tests for Sestrin 2 and Betatrophin by using ELISA technique. RESULTS: Serum Sestrin 2 significantly decreased, while serum betatrophin level significantly increased in macroalbuminuric group compared to control and other 2 diabetic groups (P value < 0.05). The cut off value of serum sestrin 2 was 0.98 ng/ml with sensitivity 99%, specificity 66% while the cut off value of serum betatrophin was > 98.25 ng/ml with sensitivity 98%, specificity 82%. Serum betatrophin positively correlated with age, fasting, 2 h postprandial, BMI, triglyceride, total cholesterol, serum creatinine, blood urea, UACR, and negatively correlated with eGFR and serum albumin. Serum Sestrin 2 positively correlated with serum albumin. BMI, serum urea, UACR and serum albumin. Serum betatrophin are found to be risk factors or predictors for diabetic nephropathy. CONCLUSIONS: Patients with DN, particularly the macroalbuminuria group, had a significant increase in betatrophin levels and a significant decrease in serum Sestrin 2 level. The function of Sestrin 2 is compromised in DN, and restoring it can reverse a series of molecular alterations with subsequent improvement of the renal functions, albuminuria and structural damage.

Asunto(s)

Proteína 8 Similar a la Angiopoyetina , Proteínas Similares a la Angiopoyetina , Diabetes Mellitus Tipo 2 , Nefropatías Diabéticas , Hormonas Peptídicas , Humanos , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/complicaciones , Nefropatías Diabéticas/sangre , Masculino , Femenino , Persona de Mediana Edad , Hormonas Peptídicas/sangre , Proteínas Similares a la Angiopoyetina/sangre , Estudios Transversales , Proteínas Nucleares/sangre , Biomarcadores/sangre , Adulto , Albuminuria/sangre , Proteínas de Choque Térmico/sangre , Anciano , Sestrinas

RESUMEN

BACKGROUND: Male reproductive functions are regulated in the hypothalamic-pituitary-gonadal (HPG) axis. Any problem in this axis would lead to the deterioration of reproductive functions. The present study aimed to investigate the effects of intracerebroventricular (icv) Spexin (SPX) infusion on the HPG axis in detail. METHODS: 40 Wistar albino rats were divided into four groups: control, sham, SPX 30 nmol and SPX 100 nmol (n=10). 30 nmol/1 µl/hour SPX was administered icv to the rats in the SPX 30 nmol group for 7 days, while rats in the SPX 100 nmol group were administered 100 nmol/1 µl/hour SPX. On the 7th day, the rats were decapitated, blood and tissue samples were collected. Serum LH, FSH and testosterone levels were determined with the ELISA method, GnRH mRNA expression level was determined in hypothalamus with the RT-PCR method. Seminiferous tubule diameter and epithelial thickness were determined with the hematoxylin-eosin staining method. RESULTS: SPX infusion was increased GnRH mRNA expression in the hypothalamus tissue independent of the dose (p<0.05). Serum LH, FSH and testosterone levels in the SPX groups were increased when compared to the control and sham groups independent of the dose (p <0.05). Histological analysis revealed that SPX infusion did not lead to any changes in seminiferous epithelial thickness, while the tubule diameter increased in the SPX groups (p<0.05). CONCLUSION: The study findings demonstrated that icv SPX infusion stimulated the HPG axis and increased the secretion of male reproductive hormones.

Asunto(s)

Hormona Folículo Estimulante , Hormona Liberadora de Gonadotropina , Sistema Hipotálamo-Hipofisario , Hormona Luteinizante , Hormonas Peptídicas , Ratas Wistar , Testículo , Testosterona , Animales , Masculino , Ratas , Testículo/efectos de los fármacos , Testículo/metabolismo , Sistema Hipotálamo-Hipofisario/efectos de los fármacos , Sistema Hipotálamo-Hipofisario/metabolismo , Testosterona/sangre , Hormona Luteinizante/sangre , Hormonas Peptídicas/administración & dosificación , Hormonas Peptídicas/metabolismo , Hormona Folículo Estimulante/sangre , Hormona Liberadora de Gonadotropina/metabolismo , Inyecciones Intraventriculares , Hipotálamo/efectos de los fármacos , Hipotálamo/metabolismo , Infusiones Intraventriculares , ARN Mensajero/metabolismo

RESUMEN

Alzheimer's disease (AD) is the most prevalent neurodegenerative disease, which is characterized by the accumulation and aggregation of amyloid in brain. Neuronostatin (NST) is an endogenous peptide hormone that participates in many fundamental neuronal processes. However, the metabolism and function of NST in neurons of AD mice are not known. In this study, by combining the structural analyses, primary cultures, knockout cells, and various assessments, the behavior, histopathology, brain-wide expression and cellular signaling pathways in the APP/PS1 mice were investigated. It was found that NST directly bound to GPR107, which was primarily expressed in neurons. NST modulated the neuronal survivability and neurite outgrowth induced by Aß via GPR107 in neurons. Intracerebroventricular (i.c.v.) administration of NST attenuated learning and memory abilities, reduced the synaptic protein levels of hippocampus, but improved amyloid plaques in the cortex and hippocampus of APP/PS1 mice. NST modulated glucose metabolism of hypothalamus-hippocampus-cortex axis in APP/PS1 mice and decreased ATP levels via the regulation of reactive oxygen species (ROS) and mitochondrial membrane potential (MMP) in response to Aß, suppressed energetic metabolism, and mitochondrial function in neurons via GPR107/protein kinase A (PKA) signaling pathway. In summary, our findings suggest that NST regulates neuronal function and brain energetic metabolism in AD mice via the GPR107/PKA signaling pathway, which can be a promising target for the treatment of AD.

Asunto(s)

Enfermedad de Alzheimer , Metabolismo Energético , Ratones Transgénicos , Neuronas , Receptores Acoplados a Proteínas G , Animales , Enfermedad de Alzheimer/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Receptores Acoplados a Proteínas G/genética , Metabolismo Energético/efectos de los fármacos , Metabolismo Energético/fisiología , Neuronas/metabolismo , Neuronas/efectos de los fármacos , Ratones , Hormonas Peptídicas/metabolismo , Hormonas Peptídicas/farmacología , Ratones Endogámicos C57BL , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Potencial de la Membrana Mitocondrial/fisiología , Hipocampo/metabolismo , Hipocampo/efectos de los fármacos , Péptidos beta-Amiloides/metabolismo , Células Cultivadas , Masculino , Humanos , Precursor de Proteína beta-Amiloide/genética , Precursor de Proteína beta-Amiloide/metabolismo

RESUMEN

Vascular smooth muscle cell (VSMCs) is one of the important cell types in artery. VSMCs stiffening may regulate vascular stiffness and contribute to the development of vulnerable plaques. Thrombin, an enzyme in coagulation system, is involved in pathological processes of atherosclerosis. Inter-alpha-trypsin inhibitor heavy chain 4 (ITIH4) plays an important role in regulating inflammation and may have cardiovascular protective effect. Therefore, the elucidation of the mechanisms underlying ITIH4-mediated VSMCs stiffening helps to provide new ideas and potential targets for the diagnosis and treatment of atherosclerosis. In this study, we used specific ITIH4 expression vector and siRNA methods to transfect VSMCs. Our results found that ITIH4 expression increased VSMCs stiffness, meanwhile, ITIH4 siRNA decreased VSMCs stiffness. ITIH4 increased acetylated α-tubulin and inhibited ERK1/2 and JNK, but not P38 MAPK. ERK inhibitor (PD98059) or JNK inhibitor (SP600125) treatment increased acetylated α-tubulin expression and cell stiffness in VSMCs. ITIH4 was downregulated by thrombin treatment, ITIH4 partly reversed the effect of thrombin on acetylated α-tubulin and VSMCs stiffness. These results indicated that ITIH4 regulated acetylated α-tubulin expression in VSMCs and was against the effects of thrombin on VSMCs stiffness. JNK and ERK signaling pathways were proved to participate in this process.

Asunto(s)

Sistema de Señalización de MAP Quinasas , Músculo Liso Vascular , Trombina , Trombina/farmacología , Trombina/metabolismo , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/citología , Músculo Liso Vascular/efectos de los fármacos , Animales , Miocitos del Músculo Liso/metabolismo , Miocitos del Músculo Liso/efectos de los fármacos , Rigidez Vascular/efectos de los fármacos , Células Cultivadas , Ratas , Humanos , Ratas Sprague-Dawley , Hormonas Peptídicas/metabolismo , Hormonas Peptídicas/farmacología , Hormonas Peptídicas/genética

RESUMEN

Patients with schizophrenia show a disproportionally increased risk of cardiovascular disease. Hypertriglyceridemia is prevalent in this population; however, how this relates to levels of remnant cholesterol, triglyceride (TG)-rich lipoprotein (TRL) particle size and composition, TG turnover, and apolipoprotein (apo) and angiopoietin-like protein (ANGPTL) concentrations is unknown. Fasting levels of cholesterol (total [TC], LDL-C, HDL-C, non-HDL-C and remnant cholesterol) and TG were determined in 110 patients diagnosed with schizophrenia, and 46 healthy controls. TRL particle size, concentration and composition, and ß-hydroxybutyrate (TG turnover marker) were assessed by NMR. Levels of apoCII, apoCIII, apoE, ANGPTL3, ANGPTL4, and ANGPTL8 were measured by ELISA, and apoCII, apoCIII and apoE were further evaluated in HDL and non-HDL fractions. Patients with schizophrenia had significantly elevated TG, TG:apoB ratio, non-HDL-C, remnant cholesterol, non-HDL-apoCII and non-HDL-apoCIII, and HDL-apoE (all P < 0.05), lower HDL-C and apoA-I (all P < 0.001), and comparable apoB, TC, TC:apoB ratio, LDL-C, ß-hydroxybutyrate, ANGPTL3, ANGPTL4 and ANGPTL8 to healthy controls. Patients had a 12.0- and 2.5-fold increase in the concentration of large and medium TRL particles respectively, but similar cholesterol:TG ratio within each particle. Plasma TG, remnant cholesterol, and large and medium TRL particle concentrations correlated strongly with apoCII, apoCIII, and apoE in the non-HDL fraction, and with apoCIII and apoE in the HDL fraction in patients with schizophrenia. Differences in TG, HDL-C, TRL particle concentrations, apoCIII, and apoE persisted after adjustment for conventional risk factors. These results are consistent with impaired TRL lipolysis and clearance in patients with schizophrenia which may be responsive to targeting apoCIII.

Asunto(s)

Apolipoproteína C-III , Apolipoproteínas E , Colesterol , Lipoproteínas , Esquizofrenia , Triglicéridos , Humanos , Esquizofrenia/sangre , Esquizofrenia/metabolismo , Masculino , Femenino , Triglicéridos/sangre , Adulto , Colesterol/sangre , Lipoproteínas/sangre , Apolipoproteína C-III/sangre , Apolipoproteínas E/sangre , Persona de Mediana Edad , Proteína 4 Similar a la Angiopoyetina/sangre , Proteínas Similares a la Angiopoyetina/sangre , Apolipoproteína C-II/sangre , Proteína 8 Similar a la Angiopoyetina , Proteína 3 Similar a la Angiopoyetina/sangre , Estudios de Casos y Controles , Hormonas Peptídicas/sangre

RESUMEN

Background: Spexin is a novel peptide hormone and has shown antinociceptive effects in experimental mice. This study is aimed at evaluating the association of serum spexin level with diabetic peripheral neuropathy (DPN) and related pain in a Chinese population. Methods: We enrolled 167 type 2 diabetes mellitus (T2DM) including 56 patients without DPN (non-DPN), 67 painless DPN, and 44 painful DPN. Serum spexin was measured using ELISA. Logistic regression models were performed to analyze the independent effects of spexin on prevalence of DPN and painful DPN. In streptozotocin (STZ)-induced diabetic mice, mechanical pain threshold was measured using electronic von Frey aesthesiometer. Human peripheral blood mononuclear cells (PBMCs) were isolated and further stimulated with lipopolysaccharide without or with spexin. The gene expression was assayed by qPCR. Results: Compared with non-DPN, serum spexin level decreased in painless DPN and further decreased in painful DPN. The odds of DPN was associated with low spexin level in T2DM, which was similar by age, sex, BMI, and diabetes duration, but attenuated in smokers. The odds of having pain was associated with decreased spexin level in DPN, which was similar by age, sex, smoking status, and diabetes duration, but attenuated in normal weight. Furthermore, we observed that mechanical pain threshold increased in spexin-treated diabetic mice. We also found that lipopolysaccharide treatment increased the mRNA level of TNF-α, IL-6, and MCP-1 in human PBMCs, while spexin treatment prevented this increase. Conclusions: These results suggested that spexin might serve as a protective factor for diabetes against neuropathology and pain-related pathogenesis.

Asunto(s)

Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Neuropatías Diabéticas , Hormonas Peptídicas , Humanos , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/sangre , Neuropatías Diabéticas/sangre , Neuropatías Diabéticas/etiología , Animales , Masculino , Persona de Mediana Edad , Femenino , Diabetes Mellitus Experimental/complicaciones , Diabetes Mellitus Experimental/sangre , Ratones , Anciano , Hormonas Peptídicas/sangre , Leucocitos Mononucleares/metabolismo , Umbral del Dolor , China/epidemiología , Ratones Endogámicos C57BL

RESUMEN

Calcitonin gene-related peptide (CGRP) and adrenomedullin 2/intermedin (AM2/IMD) play important roles in several pathologies, including cardiovascular disease, migraine and cancer. The efficacy of drugs targeting CGRP signalling axis for the treatment of migraine patients is sometimes offset by side effects (e.g. inflammation and microvascular complications, including aberrant neovascularisation in the skin). Recent studies using animal models implicate CGRP in lymphangiogenesis and lymphatic vessel function. However, whether CGRP or AM2/IMD can act directly on lymphatic endothelial cells is unknown. Here, we found that CGRP and AM2/IMD induced p44/42 MAPK phosphorylation in a time- and dose-dependent manner in primary human dermal lymphatic endothelial cells (HDLEC) in vitro, and thus directly affected these cells. These new findings reveal CGRP and AM2/IMD as novel regulators of LEC biology and warrant further investigation of their roles in the context of pathologies associated with lymphatic function in the skin and other organs, and therapies targeting CGRP signalling axis.

Asunto(s)

Adrenomedulina , Péptido Relacionado con Gen de Calcitonina , Células Endoteliales , Proteína Quinasa 1 Activada por Mitógenos , Proteína Quinasa 3 Activada por Mitógenos , Humanos , Adrenomedulina/metabolismo , Adrenomedulina/farmacología , Péptido Relacionado con Gen de Calcitonina/metabolismo , Células Cultivadas , Células Endoteliales/metabolismo , Células Endoteliales/efectos de los fármacos , Proteína Quinasa 1 Activada por Mitógenos/metabolismo , Proteína Quinasa 3 Activada por Mitógenos/metabolismo , Hormonas Peptídicas , Fosforilación/efectos de los fármacos

RESUMEN

Injury to internal organs caused by myocardial infarction (MI), although often neglected, is a very serious condition which damages internal organs especially the lungs. Changes in microcirculation can begin with acute lung injury and result in severe respiratory failure. The aim of this study was to create new approaches that will explain the pathophysiology and treatment of the disease by examining the therapeutic effects of vitamin D (VITD) and Nerolidol (NRD) on the injuries of the lungs caused by MI, and their relationship with asprosin / spexin proteins. METHODS: Six groups of seven experimental animals each were constituted. Control, VITD (only 50 IU/day during the experiment), NRD (only 100 mg/kg/day during the experiment), MI (200 mg/kg isoproterenol was administered to rats as a single dose subcutaneously), MI+VITD (200 mg/kg isoproterenol +50 IU/day) and MI+NRD (200 mg/kg isoproterenol +100 mg/kg/day) were the six (6) groups constituted. Tissues were analyzed using histopathological and immunohistochemical methods, whereas serum samples were analyzed using ELISA method. RESULTS: The result of the histopathological study for the MI group showed an observed increase in inflammatory cells, congestion, interalveolar septal thickening, erythrocyteloaded macrophages and fibrosis in the lung tissues. The treatment groups however recorded significant differences with regards to these parameters. In the immunohistochemical analysis, expressions of asprosin and spexin were observed in the smooth muscle structures and interalveolar areas of the vessels and bronchioles of the lung, as well as the bronchiole epithelium. There was no significant difference between the groups in terms of asprosin and spexin expression in the bronchiol epithelium. When immunohistochemical and serum ELISA results were examined, it was observed that asprosin levels increased significantly in the lung tissues of the MI group compared to the control group, decreased significantly in the treatment groups treated with Vitamin D and NRD after MI. While spexin decreased significantly in the MI group compared to the control group, it increased significantly in the MI+VITD group, but did not change in the MI+NRD group. CONCLUSION: It was observed that serious injuries occurred in the lungs due to myocardial infarction and that, VITD and NRD treatments had a curative effect on those injuries. It was also observed that Asprosin and Speksin proteins can have effect on mechanisms of both injury and therapy of the lung. Furthermore, the curative effects of VITD are dependent on the expression of asprosin and spexin; whereas the observation indicated that nerolidol could be effective through asprosin-dependent mechanisms and specisin by independent mechanisms.

Asunto(s)

Infarto del Miocardio , Sesquiterpenos , Vitamina D , Animales , Infarto del Miocardio/tratamiento farmacológico , Infarto del Miocardio/patología , Infarto del Miocardio/metabolismo , Sesquiterpenos/farmacología , Sesquiterpenos/uso terapéutico , Ratas , Vitamina D/farmacología , Masculino , Hormonas Peptídicas/metabolismo , Hormonas Peptídicas/farmacología , Lesión Pulmonar/tratamiento farmacológico , Lesión Pulmonar/patología , Lesión Pulmonar/etiología , Lesión Pulmonar/metabolismo , Pulmón/patología , Pulmón/efectos de los fármacos , Pulmón/metabolismo , Modelos Animales de Enfermedad , Proteínas de la Matriz Extracelular/metabolismo , Isoproterenol/farmacología , Ratas Wistar

RESUMEN

Spexin (SPX, NPQ) is a 14-amino acid neuroactive peptide identified using bioinformatics. This amino acid sequence of the mature spexin peptide has been highly conserved during species evolution and is widely distributed in the central nervous system and peripheral tissues and organs. Therefore, spexin may play a role in various biological functions. Spexin, the cognate ligand for GALR2/3, acting as a neuromodulator or endocrine signaling factor, can inhibit reproductive performance. However, controversies and gaps in knowledge persist regarding spexin-mediated regulation of animal reproductive functions. This review focuses on the hypothalamic-pituitary-gonadal axis and provides a comprehensive overview of the impact of spexin on reproduction. Through this review, we aim to enhance understanding and obtain in-depth insights into the regulation of reproduction by spexin peptides, thereby providing a scientific basis for future investigations into the molecular mechanisms underlying the influence of spexin on reproductive function. Such investigations hold potential benefits for optimizing farming practices in livestock, poultry, and fish industries.

Asunto(s)

Hormonas Peptídicas , Reproducción , Vertebrados , Animales , Reproducción/fisiología , Hormonas Peptídicas/metabolismo , Hormonas Peptídicas/fisiología , Vertebrados/fisiología , Humanos , Sistema Hipotálamo-Hipofisario/metabolismo , Sistema Hipotálamo-Hipofisario/fisiología