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1.
Growth Factors ; : 1-9, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39007914

RESUMO

This study investigated the combined effects of resistance exercise training (RET) and alternate-day calorie restriction (ADCR) on body composition, insulin resistance (IR), insulin resistance-related biomarkers (adipokine adipsin and hepatokine soluble EFGR), and weight loss in obese men. The findings revealed that RET + ADCR induced the greatest reductions in body weight, body fat percentage, and waist-to-hip ratio (WHR) compared to RET and ADCR alone (p < 0.05). Additionally, RET + ADCR resulted in the most significant improvements in IR, as measured by HOMA-IR, and in circulating levels of adipsin and soluble EFGR (p < 0.05). These findings suggest that combining RET and ADCR may be a more effective strategy for improving metabolic health, including body composition, IR, and metabolic tissues' functions, in obese men than either intervention alone.

2.
Indian J Clin Biochem ; 39(3): 415-420, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39005860

RESUMO

Adipsin is an anti-inflammatory adipokines and its altered level was seen in obesity and type II DM. Our study investigated the clinical significance of serum adipsin levels as a risk marker for type 2 diabetes and its relationships with insulin resistance and various adipo-cytokines. The study included 110 treatment-naïve T2DM cases and 100 controls of similar age and gender from northern India. Clinical, biochemical, and anthropometric characteristics were all profiled. Serum adipo-cytokines were measured using ELISA methods. Adipsin was significantly inversely correlated with body mass index (BMI), waist circumference, fasting plasma glucose, glycated haemoglobin (HbA1C), total cholesterol (TC), triglyceride (TG), homeostasis model assessment-estimated insulin resistance (HOMA-IR), tumour necrosis factor- α (TNF-α) and interleulin-6 (IL-6) and positively correlated with high-density lipoprotein cholesterol (HDL-C) and homeostasis model assessment of ß-cell function (HOMA-B) (P < 0.05). T2DM occurrence decreased with increasing concentration of adipsin with an odds ratio (OR) of 0.68 (95% CI = 0.58-0.79), P < 0.001. The area under curve (95% CI) for adipsin was 0.70 (0.63 to 0.76) with P < 0.001. The best cutoff value for adipsin to predict T2DM was < 5.50 µg/ml with 47.27% sensitivity and 82.00% specificity. FPG and WC were both independent predictors of serum adipsin levels. Our findings showed that high adipsin levels reduced the likelihood of T2DM and emerged as a potential risk marker in the prediction of T2DM.

3.
Cancer Sci ; 114(11): 4134-4144, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37622414

RESUMO

Cancer stem cells (CSCs) are a highly tumorigenic subpopulation of the cancer cells within a tumor that drive tumor initiation, progression, and therapy resistance. In general, stem cell niche provides a specific microenvironment in which stem cells are present in an undifferentiated and self-renewable state. CSC niche is a specialized tumor microenvironment for CSCs which provides cues for their maintenance and propagation. However, molecular mechanisms for the CSC-niche interaction remain to be elucidated. We have revealed that adipsin (complement factor D) and its downstream effector hepatocyte growth factor are secreted from adipocytes and enhance the CSC properties in breast cancers in which tumor initiation and progression are constantly associated with the surrounding adipose tissue. Considering that obesity, characterized by excess adipose tissue, is associated with an increased risk of multiple cancers, it is reasonably speculated that adipocyte-CSC interaction is similarly involved in many types of cancers, such as pancreas, colorectal, and ovarian cancers. In this review, various molecular mechanisms by which adipocytes regulate CSCs, including secretion of adipokines, extracellular matrix production, biosynthesis of estrogen, metabolism, and exosome, are discussed. Uncovering the roles of adipocytes in the CSC niche will propose novel strategies to treat cancers, especially those whose progression is linked to obesity.


Assuntos
Adipócitos , Neoplasias da Mama , Humanos , Feminino , Adipócitos/patologia , Neoplasias da Mama/patologia , Tecido Adiposo/patologia , Células-Tronco Neoplásicas/metabolismo , Obesidade/metabolismo , Microambiente Tumoral
4.
BMC Med ; 21(1): 197, 2023 05 26.
Artigo em Inglês | MEDLINE | ID: mdl-37237266

RESUMO

BACKGROUND: Microvascular complications are associated with an overtly increased risk of adverse outcomes in patients with diabetes including coronary microvascular injury which manifested as disruption of adherens junctions between cardiac microvascular endothelial cells (CMECs). However, particular mechanism leading to diabetic coronary microvascular hyperpermeability remains elusive. METHODS: Experimental diabetes was induced in mice with adipose tissue-specific Adipsin overexpression (AdipsinLSL/LSL-Cre) and their respective control (AdipsinLSL/LSL). In addition, cultured CMECs were subjected to high glucose/palmitic acid (HG + PA) treatment to simulate diabetes for a mechanistic approach. RESULTS: The results showed that Adipsin overexpression significantly reduced cardiac microvascular permeability, preserved coronary microvascular integrity, and increased coronary microvascular density. Adipsin overexpression also attenuated cardiac dysfunction in diabetic mice. E/A ratio, an indicator of cardiac diastolic function, was improved by Adipsin. Adipsin overexpression retarded left ventricular adverse remodeling, enhanced LVEF, and improved cardiac systolic function. Adipsin-enriched exosomes were taken up by CMECs, inhibited CMECs apoptosis, and increased CMECs proliferation under HG + PA treatment. Adipsin-enriched exosomes also accelerated wound healing, rescued cell migration defects, and promoted tube formation in response to HG + PA challenge. Furthermore, Adipsin-enriched exosomes maintained adherens junctions at endothelial cell borders and reversed endothelial hyperpermeability disrupted by HG + PA insult. Mechanistically, Adipsin blocked HG + PA-induced Src phosphorylation (Tyr416), VE-cadherin phosphorylation (Tyr685 and Tyr731), and VE-cadherin internalization, thus maintaining CMECs adherens junctions integrity. LC-MS/MS analysis and co-immunoprecipitation analysis (Co-IP) unveiled Csk as a direct downstream regulator of Adipsin. Csk knockdown increased Src phosphorylation (Tyr416) and VE-cadherin phosphorylation (Tyr685 and Tyr731), while abolishing Adipsin-induced inhibition of VE-cadherin internalization. Furthermore, Csk knockdown counteracted Adipsin-induced protective effects on endothelial hyperpermeability in vitro and endothelial barrier integrity of coronary microvessels in vivo. CONCLUSIONS: Together, these findings favor the vital role of Adipsin in the regulation of CMECs adherens junctions integrity, revealing its promises as a treatment target against diabetic coronary microvascular dysfunction. Graphical abstract depicting the mechanisms of action behind Adipsin-induced regulation of diabetic coronary microvascular dysfunction.


Assuntos
Diabetes Mellitus Experimental , Cardiomiopatias Diabéticas , Camundongos , Animais , Cardiomiopatias Diabéticas/genética , Diabetes Mellitus Experimental/complicações , Células Endoteliais , Fator D do Complemento/farmacologia , Cromatografia Líquida , Espectrometria de Massas em Tandem , Células Cultivadas
5.
BMC Musculoskelet Disord ; 24(1): 196, 2023 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-36927409

RESUMO

BACKGROUND: Apart from the positive effect of lumbar traction on structural changes within the spine in patients with low back pain, it is likely that therapeutic effects are correlated with pain biomarkers in the blood. Among them, systemic metabolic factors related to obesity may play an important role. This is the first study designed to examine the effectiveness of traction therapy in two experimental groups with considerably different BMI and to assess relationships between blood biomarkers and low back pain intensity. METHODS: In the prospective clinical trial, women suffering from chronic low back pain were allocated into the normal-weight or obesity groups. Patients in both groups underwent twenty sessions of lumbar traction therapy (30 min a day, continuous mode with a force level of 25-30% of body weight). Before and after therapy subjective assessments of pain (VAS and PPT) were performed, and serum concentrations of aggrecan chondroitin sulfate 846 epitope (CS-846), neuropeptide Y, leptin, adipsin and growth and differentiation factor 15 (GDF-15) were determined. The data were statistically evaluated for 28 women. RESULTS: After therapy, the maximal low back pain decreased in both groups, GDF-15 concentration was reduced in the normal-weight group and increased in the obesity group, and CS-846 concentration decreased in the obesity group. The sensation of PPT in the lumbar spine and mean concentrations of neuropeptide Y, leptin and adipsin did not change in both groups. However, the relationships of GDF-15, leptin, and adipsin concentrations with the perception of pain were revealed. CONCLUSION: Distinct differences between the normal-weight and obesity groups pointed on the role of excessive adipose tissue in aggravating the inflammatory processes and in the development of low back pain. Adipsin, CS-846 and GDF-15 aspire to be the low back pain biomarkers in women with obesity, but there is a need for further research to answer whether they might be considered reliable biomarkers for the prognosis and monitoring of chronic low back treatment. TRIAL REGISTRATION: NCT04507074, registered prospectively on July 6, 2020.


Assuntos
Dor Lombar , Humanos , Feminino , Dor Lombar/diagnóstico , Dor Lombar/terapia , Tração , Índice de Massa Corporal , Leptina , Fator D do Complemento , Estudos Prospectivos , Fator 15 de Diferenciação de Crescimento , Neuropeptídeo Y , Vértebras Lombares , Obesidade/complicações , Obesidade/terapia , Resultado do Tratamento
6.
BMC Ophthalmol ; 22(1): 176, 2022 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-35436912

RESUMO

BACKROUND: Diabetic retinopathy is a disease seen with microvascular complications as a result of hyperglycemia and insulin resistance. Alarin and Adipsin are molecules with a role in energy and glucose metabolism. The aim of this study was to determine plasma and aqueous levels of Alarin and Adipsin in patients with and without diabetic retinopathy to evaluate their potential roles in diabetic retinopathy. METHODS: The study included one eye from each of 20 cataract patients without diabetes (C), 20 cataract patients with diabetes and without diabetic retinopathy (DM + C), and 20 cataract patients with diabetes and diabetic retinopathy (DR + C). Plasma and aqueous humour samples were taken from all patients during the cataract operation. Alarin and Adipsin levels were examined with the enzyme-linked immunosorbent assay (ELISA) method. RESULTS: Both plasma and aqueous Alarin levels were significantly higher in the patients with diabetic retinopathy than in the control group (p < 0.001, p = 0.006). Adipsin levels were found to be significantly higher in plasma in the control group than in the DR + C group and significantly higher in aqueous in the DR + C group than in the control group (p < 0.001, p < 0.001). CONCLUSION: These findings suggest that Alarin and Adipsin may play important role in diabetic retinopathy.


Assuntos
Catarata , Fator D do Complemento/análise , Diabetes Mellitus Tipo 2 , Retinopatia Diabética , Humor Aquoso/metabolismo , Catarata/complicações , Fator D do Complemento/metabolismo , Diabetes Mellitus Tipo 2/complicações , Retinopatia Diabética/complicações , Ensaio de Imunoadsorção Enzimática , Peptídeo Semelhante a Galanina , Humanos
7.
Int J Mol Sci ; 23(4)2022 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-35216336

RESUMO

(1) Adipsin is an adipokine that may link increased fat mass and adipose tissue dysfunction to obesity-related cardiometabolic diseases. Here, we investigated whether adipsin serum concentrations and adipose tissue (AT) adipsin mRNA expression are related to parameters of AT function, obesity and type 2 diabetes (T2D). (2) Methods: A cohort of 637 individuals with a wide range of age and body weight (Age: 18-85 years; BMI: 19-70 kg/m2) with (n = 237) or without (n = 400) T2D was analyzed for serum adipsin concentrations by ELISA and visceral (VAT) and subcutaneous (SAT) adipsin mRNA expression by RT-PCR. (3) Results: Adipsin serum concentrations were significantly higher in patients with T2D compared to normoglycemic individuals. We found significant positive univariate relationships of adipsin serum concentrations with age (r = 0.282, p < 0.001), body weight (r = 0.264, p < 0.001), fasting plasma glucose (r = 0.136, p = 0.006) and leptin serum concentrations (r = 0.362, p < 0.001). Neither VAT nor SAT adipsin mRNA expression correlated with adipsin serum concentrations after adjusting for age, sex and BMI. Independent of T2D status, we found significantly higher adipsin expression in SAT compared to VAT (4) Conclusions: Our data suggest that adipsin serum concentrations are strongly related to obesity and age. However, neither circulating adipsin nor adipsin AT expression reflects parameters of impaired glucose or lipid metabolism in patients with obesity with or without T2D.


Assuntos
Tecido Adiposo/metabolismo , Fator D do Complemento/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Obesidade/metabolismo , Idoso , Glicemia/metabolismo , Índice de Massa Corporal , Feminino , Humanos , Insulina/metabolismo , Gordura Intra-Abdominal/metabolismo , Masculino , Pessoa de Meia-Idade , Circunferência da Cintura/fisiologia
8.
Am J Physiol Endocrinol Metab ; 320(1): E87-E92, 2021 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-33135458

RESUMO

Obesity is a potent risk factor for atherosclerotic morbidity and mortality. Cytokines secreted from adipose tissue, namely, adipokines, have been suggested to be actively involved in atherosclerosis. One of the most abundant adipokines, adipsin, is downregulated in obesity. It catalyzes the rate-limiting step of alternative complement activation, which is one of the three complement pathways potentially involved in inflammation in atherosclerosis. Interestingly, adipsin has been identified as a novel biomarker in human coronary artery disease. However, its role in the development of atherosclerosis remains unexplored. We crossed adipsin-/- mice onto an Ldlr-/- background [double-knockout (DKO) mice] and induced atherogenesis by high-fat and high-cholesterol feeding. Metabolic profiles were systemically characterized, and atherosclerotic plaques were measured at both aortic root and arch regions. Western blotting was conducted to assess adipsin level and complement activity. The DKO mice exhibited similar sizes of atherosclerotic lesions as Ldlr-/- control mice at both the aortic root and arch regions. Accordingly, they displayed comparable metabolic parameters, including body weight, insulin sensitivity, and lipid profiles, along with compensated complement activity. Adipsin deficiency does not impact the development of atherosclerosis in Ldlr-/- mice despite its crucial function in alternative complement activation. Therefore, it is unlikely to play an important role in mediating the risk of atherosclerotic complications in obesity.NEW & NOTEWORTHY Adipsin deficiency does not impact the development of atherosclerosis in Ldlr-/- mice despite its crucial function in alternative complement activation. Therefore, it is unlikely to play an important role in mediating the risk of atherosclerotic complications in obesity.


Assuntos
Aterosclerose/genética , Aterosclerose/metabolismo , Receptores de LDL/deficiência , Receptores de LDL/genética , Adipocinas/genética , Adipocinas/fisiologia , Animais , Aorta/patologia , Peso Corporal , Colesterol na Dieta/farmacologia , Fator D do Complemento/deficiência , Fator D do Complemento/genética , Proteínas do Sistema Complemento/metabolismo , Dieta Hiperlipídica , Resistência à Insulina/genética , Lipídeos/sangue , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Placa Aterosclerótica/patologia
9.
BMC Gastroenterol ; 21(1): 131, 2021 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-33743586

RESUMO

BACKGROUND: As a secreted adipokine, adipsin has been recently shown to play a pivotal role in metabolic disorders. However, information regarding the association of circulating adipsin with non-alcoholic fatty liver disease (NAFLD) in humans is scant. METHODS: We recruited 1163 obese adult subjects with waist circumference at least 90 cm in men and 80 cm in women from the community. Circulating adipsin levels were measured by enzyme-linked immunosorbent assay. RESULTS: Circulating adipsin levels of NAFLD subjects was decreased compared to those in non-NAFLD (p < 0.05). The prevalence of NAFLD with lower levels of serum adipsin was significantly higher than those with higher values (57.6% vs. 50.9%, p < 0.05). Circulating adipsin levels were significantly associated with decreasing levels of fasting glucose and postprandial glucose (both p < 0.001 for interaction) in NAFLD subjects but not in non-NAFLD subjects. The risk of NAFLD was significantly decreased by 21.7% [OR (95% CI): 0.783 (0.679-0.902), p < 0.001], adjusting for age, gender, current smoking, alcohol consumption, physical activity, BMI, systolic BP, fasting glucose, total cholesterol, HDL-c, HOMA-IR, and body fat mass. Importantly, subjects in the lowest quartile of circulating adipsin were 1.88 times more likely to have NAFLD than those in the highest quartile in multivariable logistic regression analyses. However, such associations with circulating adipsin were not noted for metabolic syndrome, abnormal liver enzyme and significant liver fibrosis. CONCLUSIONS: These results demonstrate that circulating adipsin levels in Chinese obese adults are negatively associated with risk of NAFLD, implying that serum adipsin levels may be a potential protective factor in NAFLD.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Adulto , Índice de Massa Corporal , Fator D do Complemento , Estudos Transversais , Feminino , Humanos , Masculino , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Obesidade/complicações , Obesidade/epidemiologia , Fatores de Risco , Circunferência da Cintura
10.
Eur J Nutr ; 60(4): 1935-1944, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32930848

RESUMO

BACKGROUND: Epidemiological studies have suggested that adipsin and visfatin are associated with the development of type 2 diabetes. This is the first study to investigate the effects of supplementation with purified anthocyanins on serum adipsin and visfatin in patients with prediabetes or newly diagnosed diabetes. METHODS: A total of 160 participants with prediabetes or newly diagnosed diabetes (40-75 years old) were given 320 mg anthocyanins or placebo daily for 12 weeks in a randomized trial. Serum adipsin, serum visfatin, lipids and glycated hemoglobin A1c (HbA1c) were measured. The areas under the curve (AUCs) for glucose, insulin and C-peptide were determined before-and after-treatment by a standard 3-h 75 g oral glucose tolerance test (OGTT). RESULTS: Relatively significant increases in serum adipsin (net change 0.15 µg/mL [0.03, 0.27], p = 0.018) and decreases in visfatin (-3.5 ng/mL [-6.69, -0.31], p = 0.032) were observed between the anthocyanins and placebo groups. We also observed significant improvements in HbA1c (-0.11% [-0.22, -0.11], p = 0.033), apolipoprotein A-1 (apo A-1) (0.12 g/L [0.03, 0.21], p = 0.012) and apolipoprotein B (apo B) (-0.07 g/L [-0.14, -0.01], p = 0.033) in response to the anthocyanins intervention. CONCLUSION: Purified anthocyanins supplementation for 12 weeks increased serum adipsin and decreased serum visfatin in patients with prediabetes or newly diagnosed diabetes. Trial registration ClinicalTrials.gov, identifier: NCT02689765.


Assuntos
Diabetes Mellitus Tipo 2 , Estado Pré-Diabético , Adulto , Idoso , Antocianinas , Glicemia , Fator D do Complemento , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hemoglobinas Glicadas , Humanos , Pessoa de Meia-Idade , Nicotinamida Fosforribosiltransferase , Estado Pré-Diabético/diagnóstico , Estado Pré-Diabético/tratamento farmacológico
11.
BMC Cardiovasc Disord ; 21(1): 517, 2021 10 25.
Artigo em Inglês | MEDLINE | ID: mdl-34696714

RESUMO

BACKGROUND: Adipsin has been identified as a secreted adipokine that plays a critical pathogenic role in metabolic disorders. However, it is not clear regarding the association of circulating adipsin with cardiovascular disease (CVD). This study will explore the association between circulating adipsin and asymptomatic carotid atherosclerosis in Chinese obese adults. METHODS: A total of 483 obese adult subjects (aged 40 years or older) were enrolled in this study. Serum adipsin concentrations and carotid intima-media thickness (CIMT) were measured to determine these associations. RESULTS: Individuals with increased CIMT and asymptomatic carotid atherosclerosis had lower levels of circulating adipsin than controls (both p < 0.05). The prevalence of asymptomatic carotid atherosclerosis was significantly higher in subjects with lower levels of serum adipsin than those with higher values (42.5% vs. 36.7%, p < 0.05). Notably, subjects in the lowest quartile of serum adipsin were 1.94 times (p = 0.059) more likely to have increased CIMT and 2.91 times (p = 0.03) more likely to have asymptomatic carotid atherosclerosis than those in the highest quartile in multivariable logistic regression analyses, adjusting for age, gender, current smoking, alcohol consumption, physical activity, BMI, systolic BP, fasting glucose, total cholesterol, HDL-c, and HOMA-IR. However, such associations with circulating adipsin were not noted for atherosclerotic plaque. CONCLUSIONS: These findings suggest that circulating adipsin concentrations are a potential marker of risks of increased CIMT and asymptomatic carotid atherosclerosis in obese Chinese adults.


Assuntos
Doenças das Artérias Carótidas/complicações , Espessura Intima-Media Carotídea , Fator D do Complemento/análise , Obesidade/complicações , Adulto , Biomarcadores/sangue , Doenças das Artérias Carótidas/sangue , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/sangue
12.
Arch Gynecol Obstet ; 304(6): 1467-1473, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-33881585

RESUMO

OBJECTIVE: In preeclampsia, there are excessive complement components expressed due to increased complement activation; therefore, this study investigated the concentration of adipsin and C9 in HIV-associated preeclampsia. METHOD: The study population (n = 76) was stratified by pregnancy type (normotensive pregnant and preeclampsia) and by HIV status. Serum was assayed for the concentration of adipsin and C9 using a Bioplex immunoassay procedure. RESULTS: Maternal weight did not differ (p = 0.1196) across the study groups. The concentration of adipsin was statistically different between the PE vs normotensive pregnant groups, irrespective of HIV status (p = 0.0439). There was no significant difference in adipsin concentration between HIV-negative vs HIV-positive groups, irrespective of pregnancy type (p = 0.6290). Additionally, there was a significant difference in adipsin concentration between HIV-negative normotensive vs HIV-negative preeclampsia (p < 0.05), as well as a difference between HIV-negative preeclampsia vs HIV-positive preeclampsia (p < 0.05). C9 protein expression was not statistically different between the normotensive and PE groups, regardless of HIV status (p = 0.5365). No statistical significance in C9 expression was found between HIV-positive vs HIV-negative groups, regardless of pregnancy type (p = 0.3166). Similarly, no statistical significance was noted across all study groups (p = 0.0774). CONCLUSION: This study demonstrates that there is a strong correlation between the up-regulation of adipsin and PE and that adipsin is a promising biomarker to use as a diagnostic tool for PE.


Assuntos
Fator D do Complemento/metabolismo , Infecções por HIV/complicações , Placenta/metabolismo , Pré-Eclâmpsia/diagnóstico , Complicações Infecciosas na Gravidez/virologia , Adulto , Biomarcadores/sangue , Pressão Sanguínea , Complemento C9/genética , Complemento C9/metabolismo , Feminino , Humanos , Pré-Eclâmpsia/sangue , Pré-Eclâmpsia/metabolismo , Gravidez , Estudos Prospectivos
13.
Int J Mol Sci ; 22(12)2021 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-34205507

RESUMO

Complement overactivation has been reported in most patients with Barraquer-Simons syndrome (BSS), a rare form of acquired partial lipodystrophy. Complement Factor D (FD) is a serine protease with a crucial role in the activation of the alternative pathway of the complement system, which is mainly synthesized by adipose tissue. However, its role in the pathogenesis of BSS has not been addressed. In this study, plasma FD concentration was measured in 13 patients with BSS, 20 patients with acquired generalized lipodystrophy, 22 patients with C3 glomerulopathy (C3G), and 50 healthy controls. Gene expression and immunohistochemistry studies were assayed using atrophied adipose tissue from a patient with BSS. We found significantly elevated FD levels in BSS cases compared with the remaining cohorts (p < 0.001). There were no significant differences in FD levels between sexes but FD was strongly and directly associated with age in BSS (r = 0.7593, p = 0.0036). A positive correlation between FD and C3 was seen in patients with C3G, characterized by decreased FD levels due to chronic C3 consumption, but no correlation was detected for BSS. Following mRNA quantification in the patient's adipose tissue, we observed decreased CFD and C3 but elevated C5 transcript levels. In contrast, the increased FD staining detected in the atrophied areas reflects the effects of persistent tissue damage on the adipose tissue, thus providing information on the ongoing pathogenic process. Our results suggest that FD could be a reliable diagnostic biomarker involved in the pathophysiology of BSS by promoting unrestrained local complement system activation in the adipose tissue environment.


Assuntos
Fator D do Complemento/metabolismo , Lipodistrofia/sangue , Adolescente , Adulto , Idoso , Biomarcadores/sangue , Estudos de Casos e Controles , Criança , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
14.
Rheumatology (Oxford) ; 59(8): 2005-2015, 2020 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-31782787

RESUMO

OBJECTIVES: Adipsin, or complement factor D, is a serine proteinase catalysing complement factor C3 breakdown, leading to the production of opsonin (C3b), membrane attack complex (C5b-C9) and anaphylatoxins (C3a and C5a). Since adipsin is potentially associated with pulmonary arterial hypertension in SSc, we investigated adipsin expression in dermal small vessels of SSc-involved skin, the mechanism regulating adipsin expression in endothelial cells, and the correlation of serum adipsin levels with SSc clinical symptoms. METHODS: Adipsin expression was assessed by immunohistochemistry with skin sections of SSc and healthy subjects. mRNA levels of target genes and transcription factor binding to the ADIPSIN promoter were evaluated by quantitative reverse transcription PCR and chromatin immunoprecipitation, respectively. Serum adipsin levels were determined by enzyme-linked immunosorbent assay. RESULTS: Adipsin expression was remarkably increased in dermal small vessels of SSc-involved skin as compared with those of healthy control skin. Consistent with the notion that Fli1 deficiency induces SSc-like phenotypes in various types of cells, FLI1 siRNA enhanced adipsin expression at protein and mRNA levels and Fli1 bound to the ADIPSIN promoter in human dermal microvascular endothelial cells. Serum adipsin levels were significantly lower in diffuse cutaneous SSc patients than in limited cutaneous SSc patients and healthy controls, and were associated positively with elevated right ventricular systolic pressure and inversely with interstitial lung disease by multivariate regression analysis. CONCLUSION: Adipsin is up-regulated at least partially by Fli1 deficiency in endothelial cells, potentially contributing to the development of pulmonary vascular involvement in SSc.


Assuntos
Fator D do Complemento/metabolismo , Células Endoteliais/metabolismo , Endotélio Vascular/metabolismo , Proteína Proto-Oncogênica c-fli-1/genética , Hipertensão Arterial Pulmonar/genética , Escleroderma Sistêmico/genética , Pele/metabolismo , Adulto , Idoso , Animais , Feminino , Inativação Gênica , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Proteína Proto-Oncogênica c-fli-1/metabolismo , Hipertensão Arterial Pulmonar/etiologia , Hipertensão Arterial Pulmonar/metabolismo , Escleroderma Sistêmico/complicações , Escleroderma Sistêmico/metabolismo , Pele/irrigação sanguínea
15.
Pak J Med Sci ; 36(7): 1495-1499, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33235563

RESUMO

OBJECTIVES: Bariatric surgery provides most substantial and sustainable weight loss measures in individuals with obesity. Caloric restriction is not only intervention, changes in hormonal secretions are also leading contributory mechanisms to reduce body weight and improve the glycaemic control. The aim of this study was to evaluate the impact of gastric sleeve surgery on plasma retinol binding protein 4 (RBP4) and adipsin levels among Saudi male obese population. METHODS: This prospective study was conducted in the Departments of Physiology and Surgery, College of Medicine, King Saud University. Thirty-three obese (BMI>38.3) male patients age ranged from 25 to 50 years were recruited. RBP4 and adipsin levels were analyzed before and 6-12 months after gastric sleeve surgery by ELISA along with plasma glucose, insulin, HOMA-IR and lipid profile. RESULTS: Circulating RBP4 levels were not significantly changed by bariatric surgery (4382.85±40.35 ng before, and 4393.28±33.13 ng after surgery, p=0.842), neither did adipsin (2949.68±46.86 pg before, and 2917.90±41.90 pg after surgery, p=0.535). Segregation of study participants into two age groups, 25-35 and 35-50 years of age, revealed that before surgery older age group (35-50) had higher RBP4 levels compared to younger group (25-35) (p=0.016). However, after surgery RBP4 levels were decreased in older group but not to a significant level (p=0.174). In younger age group after surgery, there was a near significant increase in RBP4 levels (p=0.052). There were no significant changes in RBP4 levels in both age groups after surgery (p=0.461). For adipsin, there were no significant differences before and after surgery in both age groups. Insulin, BMI and HOMA-IR index were decreased after surgery, however there was no correlation with RBP4 and adipsin levels. CONCLUSIONS: The present study findings do not suggest a role for RBP4 and adipsin in the improvement of insulin sensitivity in Saudi male obese population after gastric sleeve surgery. However, a decrease in RBP4 levels in older individuals after surgery needs further investigations to understand its effect on weight and glycemic control.

16.
BMC Endocr Disord ; 19(1): 108, 2019 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-31651303

RESUMO

BACKGROUND: The adipokine adipsin contributes to insulin resistance (IR), inflammation, and obesity, which are all regarded as high-risk factors for mild cognitive impairment (MCI) in patients with type 2 diabetes mellitus. This research aimed to uncover the role of adipsin in Chinese type 2 diabetes mellitus (T2DM) population with early cognitive dysfunction and determine whether adipsin contributes to diabetic MCI caused by IR. METHODS: In our study, 126 patients with T2DM were enrolled. The Montreal Cognitive Assessment (MoCA) was used to assess cognitive impairment. Demographic data and neuropsychological test results were evaluated. Plasma adipsin level was measured by enzyme-linked immunosorbent assay. RESULTS: The MCI group (n = 57) presented higher plasma adipsin levels compared with the healthy controls (p = 0.018). After adjustment for educational attainment, and age, begative correlations were found between plasma adipsin levels and MoCA, Mini Mental State Exam, and Verbal Fluency Test scores(r = - 0.640, p < 0.001; r = - 0.612, p < 0.001; r = - 0.288, p = 0.035; respectively). Correlation analysis demonstrated that adipsin levels were significantly positively correlated with fasting C-peptide; homeostasis model of assessment for insulin resistance (HOMA-IR) (r = 0.368, p < 0.001; r = 0.494, p < 0.001; respectively). Multivariable regression analysis further indicated that high plasma adipsin level was a significant independent determinant of MCI in the Chinese population withT2DM (p = 0.017). CONCLUSIONS: Elevated plasma adipsin level was associated with MCI in Chinese T2DM patients. Further large-scale studies should be designed to determine whether adipsin is linked to IR-associated susceptibility to early cognitive decline in T2DM patients.


Assuntos
Biomarcadores/sangue , Disfunção Cognitiva/diagnóstico , Diabetes Mellitus Tipo 2/complicações , Adulto , Idoso , Povo Asiático/psicologia , Povo Asiático/estatística & dados numéricos , Disfunção Cognitiva/sangue , Disfunção Cognitiva/etiologia , Fator D do Complemento/análise , Estudos Transversais , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Prognóstico , Fatores de Risco
17.
Ann Nutr Metab ; 74(1): 44-52, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30541001

RESUMO

BACKGROUND/AIMS: Some adipokines, such as adiponectin and leptin, have been reported to be involved in the pathogenesis of nonalcoholic fatty liver disease (NAFLD), while the association of adipsin and visfatin with NAFLD still remains unclear. This study aimed to examine the association of circulating adipsin, visfatin, and adiponectin with NAFLD in Chinese adults. METHODS: We recruited a total of 211 eligible subjects, including 100 NAFLD cases and 111 age and sex frequency-matched controls. Circulating adipsin, visfatin, and adiponection concentrations were measured by enzymatic immunoassay. Unconditional logistic regression was conducted to assess the associations between quartiles of adipokines and NAFLD. RESULTS: Compared with the controls, NAFLD cases had higher levels of adipsin and lower levels of visfatin and adiponectin. By multivariate logistic analysis, adjusting for potential confounders, circulating adipsin levels were found to be positively associated with NAFLD risk, and circulating levels of visfatin and adiponectin were inversely associated with the risk of NAFLD (all p-trend < 0.05). The ORs were 3.76 (95% CI 1.27-11.08) for adipsin, 0.30 (95% CI 0.10-0.91) for visfatin, and 0.30 (95% CI 0.10-0.88) for adiponectin comparing subjects in the highest quartile with those in the lowest. After stratified by obesity status, the association of higher adipsin with increased risk of NAFLD was only observed in nonobese group. Additionally, the inverse association between adiponectin and NAFLD was found in both groups. CONCLUSIONS: These results indicated that increased circulating levels of adipsin and decreased circulating levels of visfatin and adiponectin were independently associated with the increased risk of NAFLD.


Assuntos
Adiponectina/sangue , Citocinas/sangue , Nicotinamida Fosforribosiltransferase/sangue , Hepatopatia Gordurosa não Alcoólica/sangue , Adipocinas/sangue , Adulto , Povo Asiático , Estudos de Casos e Controles , China , Fator D do Complemento/análise , Feminino , Humanos , Masculino
18.
J Obstet Gynaecol Res ; 43(1): 30-33, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27928850

RESUMO

AIM: The purpose of the present study was to evaluate the clinical value of the rapid strip test of urinary adipsin for the quick diagnosis of pre-eclampsia. METHODS: In a multicenter diagnostic test study, we studied the diagnostic accuracy of the rapid strip test of urinary adipsin in women presenting with pre-eclampsia. A total of 204 pre-eclampsia patients and 254 healthy pregnant women were recruited for this study, respectively. The rapid strip test of urinary adipsin was used to detect the adipsin in the urine of each patient. RESULTS: The diagnostic value of the rapid strip test of urinary adipsin for pre-eclampsia was demonstrated by its high sensitivity and specificity (95.10% and 97.64%, respectively). The diagnostic accuracy was 96.51%. The consistency analysis showed that the kappa value was 0.93 compared with the gold standard diagnosis of pre-eclampsia. CONCLUSION: The rapid strip test of urinary adipsin is a non-invasive test for the diagnosis of pre-eclampsia with high sensitivity and specificity. It could help the quick diagnosis of pre-eclampsia in clinical practice greatly.


Assuntos
Pré-Eclâmpsia/diagnóstico , Adulto , Fator D do Complemento/urina , Feminino , Humanos , Pré-Eclâmpsia/urina , Gravidez , Fitas Reagentes , Sensibilidade e Especificidade
19.
Rheumatology (Oxford) ; 55(4): 680-8, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26660640

RESUMO

OBJECTIVE: Limited studies have explored the association between adipokines and knee OA structural progression using quantitative MRI (qMRI), and very few have included total knee replacement (TKR) as a disease outcome. The objective of this study was to compare serum levels of five adipokines to cartilage volume loss (CVL) and investigate their predictive value for TKR. METHODS: The according-to-protocol population (n = 138) of a knee OA trial was used. Serum levels of adipsin (complement factor D), leptin, adiponectin, resistin and serpin E1, and cartilage volume were determined at baseline and 24 months with specific ELISAs and qMRI, respectively. Study knee TKR incidence up to 4 years post-trial was also assessed. RESULTS: Greater baseline values of adipsin and leptin correlated with increased CVL in the global knee and medial femur (P ⩽ 0.032) and of adipsin in the lateral compartment and femur (P ⩽ 0.028). Adiponectin showed an inverse correlation in the medial compartment and femur (P ⩽ 0.027). Resistin and serpin E1 were not associated with CVL. Multivariate analyses revealed that patients in the highest tertile at baseline of adipsin presented a greater odds ratio of CVL in the lateral compartment and femur (⩾2.87; P ⩽ 0.011), and those in the highest tertile of leptin in the medial compartment (2.78; P = 0.038). Most clinically relevant, patients in the highest tertile of adipsin or leptin at baseline had significantly greater incidence of TKR (P = 0.027). CONCLUSION: Data demonstrate that both adipsin and leptin predict greater CVL over time in the lateral and medial compartment, respectively. Importantly, this study also demonstrates that higher baseline levels of adipsin or leptin are associated with higher incidence of TKR.


Assuntos
Artroplastia do Joelho , Leptina/sangue , Osteoartrite do Joelho/diagnóstico , Idoso , Biomarcadores/sangue , Índice de Massa Corporal , Cartilagem Articular/patologia , Fator D do Complemento/metabolismo , Progressão da Doença , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Osteoartrite do Joelho/sangue , Osteoartrite do Joelho/patologia , Osteoartrite do Joelho/cirurgia , Índice de Gravidade de Doença
20.
J Biol Chem ; 288(43): 31400-8, 2013 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-24036114

RESUMO

Mutations in matrix Gla protein (MGP) have been correlated with vascular calcification. In the mouse model, MGP null vascular disease presents as calcifying cartilaginous lesions and mineral deposition along elastin lamellae (elastocalcinosis). Here we examined the mechanisms underlying both of these manifestations. Genetic ablation of enzyme transglutaminase 2 (TG2) in Mgp(-/-) mice dramatically reduced the size of cartilaginous lesions in the aortic media, attenuated calcium accrual more than 2-fold, and doubled longevity as compared with control Mgp(-/-) animals. Nonetheless, the Mgp(-/-);Tgm2(-/-) mice still died prematurely as compared with wild-type and retained the elastocalcinosis phenotype. This pathology in Mgp(-/-) animals was developmentally preceded by extensive fragmentation of elastic lamellae and associated with elevated serine elastase activity in aortic tissue and vascular smooth muscle cells. Systematic gene expression analysis followed by an immunoprecipitation study identified adipsin as the major elastase that is induced in the Mgp(-/-) vascular smooth muscle even in the TG2 null background. These results reveal a central role for TG2 in chondrogenic transformation of vascular smooth muscle and implicate adipsin in elastin fragmentation and ensuing elastocalcinosis. The importance of elastin calcification in MGP null vascular disease is highlighted by significant residual vascular calcification and mortality in Mgp(-/-);Tgm2(-/-) mice with reduced cartilaginous lesions. Our studies identify two potential therapeutic targets in vascular calcification associated with MGP dysfunction and emphasize the need for a comprehensive approach to this multifaceted disorder.


Assuntos
Doenças da Aorta/metabolismo , Proteínas de Ligação ao Cálcio/metabolismo , Elastina/metabolismo , Proteínas da Matriz Extracelular/metabolismo , Proteínas de Ligação ao GTP/metabolismo , Transglutaminases/metabolismo , Calcificação Vascular/metabolismo , Animais , Doenças da Aorta/genética , Doenças da Aorta/patologia , Proteínas de Ligação ao Cálcio/genética , Fator D do Complemento/genética , Fator D do Complemento/metabolismo , Elastina/genética , Proteínas da Matriz Extracelular/genética , Proteínas de Ligação ao GTP/genética , Camundongos , Camundongos Knockout , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/patologia , Miócitos de Músculo Liso/metabolismo , Miócitos de Músculo Liso/patologia , Proteína 2 Glutamina gama-Glutamiltransferase , Transglutaminases/genética , Calcificação Vascular/genética , Calcificação Vascular/patologia , Proteína de Matriz Gla
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