RESUMO
The aim of this study was to investigate the potential relationship between acylation-stimulating protein (ASP), insulin resistance, lipometabolism, the intrauterine metabolic environment and fetal growth in well-controlled gestational diabetes mellitus (GDM) women. A total of 55 well-controlled GDM women, 66 pregnant women with normal glucose tolerance (NGT) and their newborns, were included in this study. Fasting maternal and cord blood ASP, serum lipid profiles, glucose level, insulin level, HOMA-IR, in addition to neonatal anthropometry data, were measured. Maternal blood ASP in GDM is higher than that in NGT. In the GDM group, maternal blood ASP has a positive correlation with TG, FFA and HOMA-IR. Maternal and cord blood ASP levels of LGA fetuses correlate with elevated birth weight and SF4. Similarly, cord blood ASP levels of LGA fetuses also correlate with birth weight and SF4 in the NGT group. The maternal blood ASP level of GDM mothers is associated with lipometabolism, insulin resistance and LGA fetal growth. Nevertheless, the cord blood ASP level correlates with FFA of GDM mothers, LGA fetal growth of GDM and NGT mothers. ASP may be a biomarker for evaluating insulin resistance of GDM and LGA fetal growth.
Assuntos
Complemento C3a/metabolismo , Diabetes Gestacional , Sangue Fetal/metabolismo , Desenvolvimento Fetal , Resistência à Insulina , Metabolismo dos Lipídeos , Adulto , Anafilatoxinas/metabolismo , Peso ao Nascer , Glicemia/metabolismo , Índice de Massa Corporal , Estudos de Casos e Controles , China , Diabetes Gestacional/diagnóstico , Diabetes Gestacional/metabolismo , Feminino , Teste de Tolerância a Glucose/métodos , Humanos , Recém-Nascido , Gravidez , Estatística como AssuntoRESUMO
AIMS: To evaluate circulating adipokines in people with ketosis-prone diabetes, a heterogeneous disorder characterized by unprovoked ketoacidosis in people with previously unrecognized diabetes. METHODS: Patients presenting with ketoacidosis with no previous diabetes diagnosis were compared with patients with previously established Type 1 diabetes. Baseline assessments of autoimmune status (A+/A-), and ß-cell function (B+/B-), as well as leptin and adiponectin levels during a standardized mixed-meal tolerance test of 120 min, were performed. In all, 20 patients with heterogeneous ketosis-prone diabetes and 12 patients with Type 1 diabetes were evaluated at baseline, 12 and 24 months. RESULTS: At baseline, during a mixed-meal tolerance test, glucose and adiponectin concentrations were lower in patients with ketosis-prone diabetes than in those with Type 1 diabetes (P = 0.0023 and P < 0.0001, respectively), whereas C-peptide concentrations were higher, with no significant difference in leptin concentrations. Within 12 months, 11 patients with ketosis-prone diabetes (all A-/B+) were discontinued from insulin treatment (ketosis-prone diabetes - insulin group), while nine patients (four A-B-, four A+B- and one A-B+) were maintained on insulin (ketosis-prone diabetes + insulin group). Fasting C-peptide levels increased significantly over 24 months in the ketosis-prone diabetes - insulin group (P = 0.01), while HbA1c levels decreased (P < 0.0001). Overall, the ketosis-prone diabetes - insulin group had a higher BMI (P = 0.018), yet a lower fasting glucose concentration (P = 0.003) compared with the ketosis-prone diabetes + insulin group. Over 24 months, the mixed-meal tolerance test area-under-the-curve of C-peptide increased in the ketosis-prone diabetes - insulin group, with no change in ketosis-prone diabetes + insulin (P < 0.0001). At 24 months, in spite of the higher BMI in the ketosis-prone diabetes - insulin group, mixed-meal tolerance test glucose and leptin concentrations were significantly lower (P < 0.0001 and P = 0.017, respectively), while adiponectin levels were higher (P = 0.023) compared with the ketosis-prone diabetes + insulin group. CONCLUSIONS: In spite of the higher BMI in the ketosis-prone diabetes - insulin group, lower leptin and higher adiponectin levels may contribute to improved ß-cell function and insulin sensitivity, as evidenced by lower glucose and higher C-peptide levels. This allows insulin therapy to be withdrawn.
Assuntos
Adiponectina/sangue , Glicemia/metabolismo , Peptídeo C/sangue , Diabetes Mellitus Tipo 1/sangue , Leptina/sangue , Adolescente , Adulto , Índice de Massa Corporal , Diabetes Mellitus Tipo 1/fisiopatologia , Feminino , Seguimentos , Hemoglobinas Glicadas/metabolismo , Humanos , Resistência à Insulina/fisiologia , Células Secretoras de Insulina/fisiologia , Masculino , Pessoa de Meia-Idade , Período Pós-Prandial , Estudos Prospectivos , Fatores de Tempo , Adulto JovemRESUMO
Obesity and related metabolic diseases are associated with chronic low-grade inflammation, characterized by increased pro-inflammatory proteins. Several studies have demonstrated increases in acylation stimulating protein (ASP) and its precursor protein C3 in obesity, diabetes and dyslipidemia. To evaluate the effects of acute inflammatory factors and adipokines on ASP production and potential mechanisms of action, 3T3-L1 adipocytes were treated for 24 h with adipokines, cytokines, macrophage-conditioned media and direct co-culture with J774 macrophages. ASP and C3 in the media were evaluated in relation to changes in adipocyte lipid metabolism (cellular triglyceride stores). Leptin, adiponectin, IL-10, LPS and TNF-α increased ASP production (151%, 153%, 190%, 318%, 134%, P<0.05, respectively,). C5a and RANTES (Regulated and normal T cell expressed and secreted) decreased ASP production ( - 34%, - 47%, P<0.05), which was also associated with a decrease in the precursor protein C3 ( - 39% to - 51%, P<0.01), while keratinocyte chemoattractant (KC; murine IL-8 ortholog) had no effect on ASP and C3 secretion. By contrast, apelin, omentin and visfatin also decreased ASP ( - 27%, - 49%, - 22%, P<0.05), but without changes in precursor protein C3 secretion. Macrophage-conditioned media alone had little effect on C3 or ASP, while co-culture of adipocytes with macrophages markedly increased ASP and C3 production (272%, 167%, P<0.05). These in vitro results suggest various metabolic hormones and inflammatory factors can affect ASP production through increased precursor C3 production and/or by changing the rate of C3 conversion to ASP. As an adipokine, ASP could constitute a new link between adipocytes and macrophages.
Assuntos
Adipócitos/efeitos dos fármacos , Adipócitos/imunologia , Adipocinas/farmacologia , Complemento C3a/biossíntese , Inflamação/imunologia , Inflamação/metabolismo , Células 3T3-L1 , Adipócitos/metabolismo , Adiponectina/farmacologia , Animais , Biomarcadores , Linhagem Celular , Quimiocina CCL5/farmacologia , Técnicas de Cocultura , Complemento C5a/farmacologia , Meios de Cultivo Condicionados , Interleucina-10/farmacologia , Leptina/farmacologia , Metabolismo dos Lipídeos , Lipopolissacarídeos/farmacologia , Macrófagos/imunologia , Macrófagos/metabolismo , Camundongos , Fator de Necrose Tumoral alfa/farmacologiaRESUMO
BACKGROUND: Postoperative liver dysfunction is the major source of morbidity and mortality in patients undergoing partial hepatectomy. This study tested the benefits of a metabolic support protocol based on insulin infusion, for reducing liver dysfunction following hepatic resection. METHODS: Consecutive consenting patients scheduled for liver resection were randomized to receive preoperative dextrose infusion followed by insulin therapy using the hyperinsulinaemic normoglycaemic clamp protocol (n = 29) or standard therapy (control group, n = 27). Patients in the insulin therapy group followed a strict dietary regimen for 24 h before surgery. Intravenous dextrose was started at 2 mg per kg per min the night before and continued until surgery. Hyperinsulinaemic therapy for a total of 24 h was initiated at 2 munits per kg per min at induction of anaesthesia, and continued at 1 munit per kg per min after surgery. Normoglycaemia was maintained (3.5-6.0 mmol/l). Control subjects received no additional dietary supplement and a conventional insulin sliding scale during fasting. All patients were tested serially to evaluate liver function using the Schindl score. Liver tissue samples were collected at two time points during surgery to measure glycogen levels. RESULTS: Demographics were similar in the two groups. More liver dysfunction occurred in the control cohort (liver dysfunction score range 0-8 versus 0-4 with insulin therapy; P = 0.031). Median (interquartile range) liver glycogen content was 278 (153-312) and 431 (334-459) µmol/g respectively (P = 0.011). The number of complications rose with increasing severity of postoperative liver dysfunction (P = 0.032) CONCLUSION: The glucose-insulin protocol reduced postoperative liver dysfunction and improved liver glycogen content. REGISTRATION NUMBER: NCT00774098 (http://www.clinicaltrials.gov).
Assuntos
Glucose/administração & dosagem , Hepatectomia/métodos , Hipoglicemiantes/administração & dosagem , Insulina Regular Humana/administração & dosagem , Hepatopatias/prevenção & controle , Complicações Pós-Operatórias/prevenção & controle , Administração Cutânea , Adulto , Idoso , Glicemia , Hepatectomia/efeitos adversos , Humanos , Infusões Intravenosas , Hepatopatias/metabolismo , Glicogênio Hepático/metabolismo , Pessoa de Meia-Idade , Assistência Perioperatória/métodos , Cuidados Pré-Operatórios/métodos , Adulto JovemRESUMO
OBJECTIVE: Several gastrointestinal peptides are now recognized to have target functions beyond the intestinal wall, including effects on adipocytes. Secretin (SEC), one of the first identified, has not been evaluated in this context. METHODS: Using cultured 3T3-L1 preadipocytes, adipocytes and primary rat adipocytes we evaluated the effect of SEC on cell proliferation, mitochondrial activity, differentiation, triglyceride (TG) synthesis, lipolysis as well expression of the SEC receptor (SCTR) in rodent and human adipose tissues. RESULTS: In preadipocytes, SEC significantly increased mitochondrial activity (115%; P<0.01), thymidine incorporation (149.7%; P<0.05) and C/EBPß expression (123.4%; P<0.05). During standard differentiation, SCTR mRNA increased up to a maximum of ninefold (P<0.001). In human adipose tissue, SCTR correlated with body mass index and plasma insulin, and SCTR mRNA expression was also detected in rat adipose tissues. SEC supplementation during differentiation enhanced TG accumulation (+138%; P<0.01). In mature adipocytes, SEC increased fatty acid (FA) uptake (186%; P<0.01), adiponectin and monocyte chemotactic protein-1 secretion (+142% and +149%, respectively; P<0.05) and mRNA expression of PPARγ (+206%; P<0.01), FABP4 (+164%; P<0.001), DGAT-1 (+144%; P<0.01), adiponectin (+138%; P<0.001) and CD36 (+149%; P<0.05). In primary rat adipocytes, SEC also increased FA uptake (137%; P<0.05). Pretreatment with a SEC antagonist impaired SEC-induced FA uptake and cAMP accumulation. SEC treatment simultaneously stimulated lipolysis measured as glycerol release in 3T3-L1 adipocytes and rat adipose tissue. CONCLUSION: The present results suggest that SEC is a potent modulator of adipocyte functions, demonstrating overall a role in enhanced substrate cycling.
Assuntos
Adipócitos/metabolismo , Tecido Adiposo/metabolismo , Fator de Crescimento Insulin-Like I/metabolismo , Obesidade/metabolismo , Secretina/metabolismo , Células 3T3-L1/efeitos dos fármacos , Células 3T3-L1/metabolismo , Adipócitos/efeitos dos fármacos , Tecido Adiposo/efeitos dos fármacos , Animais , Diferenciação Celular , Proliferação de Células , Células Cultivadas , Feminino , Humanos , Lipólise , Masculino , Camundongos , Mitocôndrias/metabolismo , Obesidade/tratamento farmacológico , Ratos , Secretina/farmacologia , Triglicerídeos/metabolismoRESUMO
OBJECTIVE: The mechanisms involved in early resolution of insulin resistance and type 2 diabetes mellitus after biliopancreatic diversion with duodenal switch (BPD-DS) surgery are still unknown. We evaluated early effects of BPD-DS on plasma acylation stimulating protein (ASP), an adipokine involved in lipid and glucose metabolism. SUBJECTS: 32 non-diabetic and 22 diabetic severely obese women (BMIî¶40 kg m(-2)) were evaluated for body composition and plasma parameters before, 24 h, 5 days, 6 and 12 months after surgery. RESULTS: Within the early postoperative period (24 h), ASP decreased 25 and 30% in non-diabetic and diabetic women, respectively (P<0.001). Twenty-four hours after surgery, triglyceride, cholesterol, HDL-Chol, LDL-Chol and C3 also decreased, while glucose, insulin and high-sensitivity C-reactive protein (hsCRP) increased (all P<0.001). By 5 days, without significant weight loss, the decreases in ASP, cholesterol, HDL-Chol and LDL-Chol levels were all maintained. At this time, glucose, insulin and HOMA-IR also decreased 11 to 52% (all P<0.001). At 6 and 12 months, with pronounced weight loss and decreased per cent fat mass, there were further decreases in ASP (maximal -56% non-diabetic, -61% diabetic, P<0.001), as well as in glucose, insulin, HOMA-IR, triglyceride, cholesterol, LDL-Chol, HDL-Chol and hsCRP levels. Improved insulin resistance/diabetes at 5 days was predicted by 24 h changes as follows: per cent change ASP, HDL-Chol, hsCRP and total cholesterol predicted HOMA-IR (5 days) (r(2)=0.454, P<0.001), and per cent change ASP, HDL-Chol and hsCRP predicted change (5 days vs baseline) in HOMA-IR (r(2)=0.351, P<0.001). CONCLUSION: Acute postoperative decreases in ASP are associated with early improvement of insulin resistance/diabetes after BPD-DS surgery.
RESUMO
BACKGROUND AND AIMS: Atenolol is a beta-1 adrenergic antagonist commonly prescribed for the treatment of systemic hypertension or coronary artery disease yet its use in individuals with type 2 diabetes mellitus (T2DM) is controversial due to potentially negative side effects on insulin resistance. Non-esterified fatty acid (NEFA) metabolism is altered in T2DM especially under conditions of metabolic stress such as exercise or the postprandial state. We evaluated atenolol effects on circulating NEFA and related hormones in men with T2DM during acute cardiorespiratory exercise in both the fasting and postprandial state, including the adipokine acylation stimulating protein (ASP) which stimulates adipose tissue NEFA uptake. METHODS AND RESULTS: Ten men with T2DM underwent four 1-h exercise sessions at 60% of their maximal oxygen uptake (VO(2max)) under the following conditions: 1) fasting (F), and 2) 2 h postprandial (PP) without medication; and 3) fasting (F-Atenolol), and 4) 2 h postprandial (PP-Atenolol) after a one-week treatment with atenolol. Results were tested for the effects of atenolol via two-way ANOVA for the F vs F-Atenolol and PP vs PP-Atenolol states separately. Atenolol treatment decreased fasting and postprandial glycerol (p < 0.0001) and NEFA (p < 0.0001), postprandial epinephrine (p = 0.048), postprandial cortisol (p = 0.02), postprandial ASP (p = 0.04) and postprandial dopamine (p < 0.004). CONCLUSION: Atenolol alters fatty acid metabolism and associated metabolic hormones including ASP during exercise in men with T2DM and its effects are more apparent during conditions of stress such as the postprandial state, acute exercise and obesity.
Assuntos
Antagonistas de Receptores Adrenérgicos beta 1/farmacologia , Atenolol/farmacologia , Diabetes Mellitus Tipo 2/fisiopatologia , Exercício Físico/fisiologia , Ácidos Graxos não Esterificados/sangue , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Adulto , Complemento C3 , Estudos Cross-Over , Dopamina/sangue , Ingestão de Energia , Epinefrina/sangue , Jejum , Glicerol/sangue , Humanos , Hidrocortisona/sangue , Masculino , Pessoa de Meia-Idade , Oxigênio/metabolismo , Período Pós-PrandialRESUMO
Today, cardiovascular diseases (CVD) remain the principal cause of death in industrialized countries and are linked to obesity and metabolic syndrome. Metabolic syndrome is characterized by changes in arterial blood pressure, glucose metabolism, lipid and lipoprotein profiles in addition to inflammation. Adipose tissue produces many cytokines and secretory factors termed adipokines. Intra-abdominal (visceral) adipose tissue in particular, rather than peripheral, appears to be associated with global cardiometabolic risk. The present article summarizes information on five recently discovered adipokines: vaspin, visfatin, apelin, acylation stimulating protein (ASP) and retinol-binding protein 4 (RBP4) and their potential beneficial or deleterious roles in obesity and atherosclerosis. Vaspin may have antiatherogenic effects through its potential insulin-sensitizing properties. Similarly, visfatin has been suggested to enhance insulin sensitivity, but its potential role in plaque destabilization may counteract this. Apelin, via inhibition of food intake, and increases in physical activity and body temperature, may promote weight loss, resulting in a beneficial antiatherogenic effect. Further, favourable effects on vasodilatation and blood pressure add to this positive effect. Considering its increased levels in subjects with demonstrated atherosclerosis, RBP4 may constitute a biomarker. Lastly, ASP, often increased in obesity and metabolic disorders, may be contributing to efficient lipid storage, and decreasing or blocking ASP may provide a potential antiobesity target. Adipokines may further contribute to obesity-atherosclerosis relationships, the full understanding of which will require further research.
Assuntos
Adipocinas/metabolismo , Aterosclerose/metabolismo , Obesidade/metabolismo , Tecido Adiposo/metabolismo , Tecido Adiposo/fisiopatologia , Feminino , Humanos , Masculino , Síndrome Metabólica/metabolismo , Síndrome Metabólica/fisiopatologia , Obesidade/fisiopatologiaRESUMO
Acylation stimulating protein (ASP) is a potent lipogenic factor produced from adipocytes. Plasma ASP levels were shown to increase in obesity, diabetes mellitus type II and dyslipidemia, and decrease after weight loss and fasting. Growing evidence suggests that ASP may significantly contribute to subcutaneous fat storage in females. In vitro, ASP stimulated triglyceride synthesis to a larger extent in subcutaneous compared with omental adipocytes. The ASP receptor binding affinity to plasma membranes prepared from adipose tissue showed higher binding affinity to plasma membranes from female adipose tissue compared with male adipose tissue, and was more pronounced to subcutaneous compared with omental plasma membranes. Human studies demonstrated that postprandial triglyceride clearance predicted by ASP levels was more efficient in women than in men. In mice, postprandial triglyceride clearance, with intraperitoneal ASP administration, was faster in females compared with males. The ASP deficient mice were resistant to weight gain and had reduced fat mass that was more pronounced in females. Recent findings in humans and mice point to a significant association between progesterone and ASP variations in females. In this review, we highlight findings, to date, linking ASP to physiological and hormonal alterations that may contribute to subcutaneous fat distribution typical to females.
Assuntos
Peptídeos e Proteínas de Sinalização Intercelular/sangue , Lipogênese , Acilação , Adipócitos/metabolismo , Animais , Complemento C3 , Feminino , Hormônios Esteroides Gonadais/metabolismo , Humanos , Masculino , Camundongos , Período Pós-Prandial , Fatores Sexuais , Gordura Subcutânea Abdominal/metabolismo , Triglicerídeos/sangue , Aumento de PesoRESUMO
BACKGROUND/OBJECTIVES: Acylation-stimulating protein (ASP) is an adipose tissue-derived hormone, which stimulates glucose and free fatty acid (FFA) uptake into adipocytes. Changes in ASP metabolism are associated with alterations in lipid metabolism. As postnatal catch-up growth has been associated with dyslipidaemia in later life, we investigated the association between ASP and birth size, adult size and different growth patterns during childhood. METHODS: The associations were investigated by multiple regression analyses in 285 young adults, aged 18-24. Subsequently, differences in ASP were analysed in four clinically relevant subgroups, young adults either born small for gestational age with short stature (SGA-S) or with catch-up growth (SGA-CU), or born appropriate for gestational age with idiopathic short stature (ISS) or with normal stature (controls). RESULTS: Weight gain during childhood, particularly fat accumulation, was positively related to ASP levels in early adulthood, independent of birth size, age and gender. Foetal growth, reflected by birth size, was not related to ASP levels. Between the subgroups, no differences in ASP were found, but SGA-CU and ISS subjects had significantly higher levels of FFA. CONCLUSION: Exaggerated weight gain during childhood, but not foetal growth, contributes to alterations in ASP metabolism, which may be associated with impaired FFA uptake and delayed triglycerides clearance. Therefore, exaggerated weight gain during childhood should be prevented.
Assuntos
Desenvolvimento Infantil/fisiologia , Peptídeos e Proteínas de Sinalização Intercelular/sangue , Adolescente , Adulto , Peso ao Nascer/fisiologia , Tamanho Corporal/fisiologia , Estudos de Casos e Controles , Criança , Complemento C3 , Feminino , Transtornos do Crescimento/sangue , Transtornos do Crescimento/metabolismo , Humanos , Recém-Nascido , Recém-Nascido Pequeno para a Idade Gestacional/sangue , Recém-Nascido Pequeno para a Idade Gestacional/metabolismo , Resistência à Insulina/fisiologia , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Lipídeos/sangue , Masculino , Aumento de Peso/fisiologia , Adulto JovemRESUMO
BACKGROUND AND OBJECTIVES: By studying cardiometabolic risk factors in children born after maternal biliopancreatic diversion bariatric surgery (AMS) compared with those in children born before maternal surgery (BMS), we tested the hypothesis that significant maternal weight loss may modify obesity-related factors transmitted via the intrauterine environment. DESIGN: Anthropometry and fasting blood levels were studied in 49 mothers who had lost 36 +/- 1.8% body weight sustained for 12 +/- 0.8 yr and their 111 children (54 BMS and 57 AMS) aged 2.5-26 yr. RESULTS: AMS children had lower birth weight (2.9 +/- 0.1 AMS vs. 3.3 +/- 0.1 kg BMS, P = 0.003) associated with a reduced prevalence of macrosomia (1.8 AMS vs. 14.8% BMS, P = 0.03) with no difference in underweight. At the time of follow-up, AMS children exhibited 3-fold lower prevalence of severe obesity (11 vs. 35%, P = 0.004), greater insulin sensitivity (homeostasis model assessment of insulin resistance index 3.4 +/- 0.3 vs. 4.8 +/- 0.5, P = 0.02), improved lipid profile (cholesterol/high-density lipoprotein cholesterol 2.96 +/- 0.11 vs 3.40 +/- 0.18, P = 0.03; high-density lipoprotein cholesterol 1.50 +/- 0.05 vs. 1.35 +/- 0.05 mmol/liter, P = 0.04), lower C-reactive protein (0.88 +/- 0.17 vs. 2.00 +/- 0.34 microg/ml, P = 0.004), and leptin (11.5 +/- 1.5 vs.19.7 +/- 2.5 ng/ml, P = 0.005) and increased ghrelin (1.28 +/- 0.06 vs.1.03 +/- 0.06 ng/ml, P = 0.005) than BMS offspring (AMS vs. BMS, respectively, for all). CONCLUSIONS: This unique study of children aged 2.5-26 yr born before and after maternal antiobesity surgery demonstrated improvements in cardiometabolic markers sustained into adolescence, attributable to an improved intrauterine environment.
Assuntos
Cirurgia Bariátrica/efeitos adversos , Peso ao Nascer/genética , Obesidade/genética , Tamanho Corporal/genética , Estudos Transversais , Feminino , Macrossomia Fetal/epidemiologia , Macrossomia Fetal/genética , Seguimentos , Humanos , Recém-Nascido de Baixo Peso , Recém-Nascido , Gravidez , Útero/fisiologia , Redução de PesoRESUMO
OBJECTIVE: Resistin has been linked with obesity and hypothesized as a potential marker of insulin resistance in addition to being linked with acute inflammation. However, these links are still highly controversial in humans. Our goal was to examine resistin levels in relation to obesity, insulin resistance and inflammation markers in a large population of Asian children and adolescents. METHODS: Children and adolescents (n=3472) aged 6-18 years, boys (n=1765) and girls (n=1707), were assessed for body size parameters, pubertal development, blood lipids, glucose, insulin, resistin, C-reactive protein (CRP), adiponectin and complement C3 (C3) levels. RESULTS: Resistin increased with central obesity in both genders but not with simple adiposity in boys. Several markers associated with central obesity correlated in a gender-specific fashion with plasma resistin. Waist circumference, fat-mass percentage, waist-to-height ratio and body mass index (BMI) positively correlated with resistin in both genders. Blood lipids such as triglycerides, nonesterified fatty acids (NEFA) and low-density lipoprotein cholesterol, diastolic and systolic blood pressure correlated positively with resistin in boys. NEFA, high-density lipoprotein cholesterol (negatively) and inflammation markers, such as CRP and C3, positively correlated with resistin in girls. There was no correlation between resistin and adiponectin, and no association of adiponectin with resistin quintiles in either boys or girls. In both boys and girls, resistin tended to decrease with age, with girls having higher levels than boys. Few indices of insulin resistance were linked with plasma resistin in either gender. CONCLUSION: In this population, plasma resistin levels are a weak biochemical marker of metabolic dysfunction defined by central obesity, adiposity and inflammation and does not predict insulin resistance. Only a small proportion of resistin variation can be explained by factors related to metabolic syndrome, suggesting that resistin is not strongly implicated in a concentration-dependent fashion in any of the examined pathologies.
Assuntos
Adiposidade/fisiologia , Resistência à Insulina/fisiologia , Síndrome Metabólica/sangue , Obesidade Abdominal/sangue , Resistina/sangue , Adolescente , Fatores Etários , Antropometria , Povo Asiático/etnologia , Biomarcadores/sangue , Criança , Estudos Transversais , Feminino , Humanos , Inflamação/sangue , Masculino , Valor Preditivo dos Testes , Fatores SexuaisRESUMO
AIM: Both type 1 and 2 diabetes are associated with differential regulation of leptin, adiponectin and ASP. Our aim was to examine whether or not acute hyperinsulinaemia and/or hyperglycaemia per se have differential regulation of these hormones in healthy subjects. METHODS: We examined changes in leptin, adiponectin and ASP concentrations and subcutaneous white adipose tissue mRNA expression with 3-hour hyperinsulinaemic (HI, n=10), hyperglycaemic (HG, n=7) and hyperinsulinaemic-hyperglycaemic (HGHI, n=8) clamps in healthy lean young men. As somatostatin was used for the HG and HGHI clamps, a control somatostatin clamp was carried out (n=4). Changes in the expression of HKII and p85alpha Pi3K were examined as positive controls for the induction of gene expression by the insulin pathway. RESULTS: HI, HG and HGHI clamps increased expression of HKII and p85alpha Pi3K while somatostatin did not. The HI clamp decreased serum adiponectin (-15%, P<0.001) and increased serum leptin (+11%, P=0.031), while the HG clamp reduced serum leptin (-20%, P=0.003). The HGHI clamp increased serum ASP (+21%, P=0.047) and expression of C3 (+26%, P=0.018) and leptin (+50%, P=0.024). Interestingly, the control somatostatin clamp suppressed both serum leptin (-17%, P=0.043) and adiponectin (-7%, P=0.020). CONCLUSION: HG and/or HI per se regulated the concentrations and expression of leptin, adiponectin and ASP in healthy lean young men, suggesting a contribution to dysregulation of these hormones in diabetes.
Assuntos
Glicemia/metabolismo , Complemento C3/metabolismo , Hiperglicemia/metabolismo , Hiperinsulinismo/metabolismo , Insulina/sangue , Leptina/metabolismo , Adiponectina/sangue , Adiponectina/metabolismo , Tecido Adiposo Branco/metabolismo , Adulto , Diabetes Mellitus Tipo 1/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Técnica Clamp de Glucose , Humanos , Insulina/administração & dosagem , Leptina/sangue , Masculino , Somatostatina/administração & dosagemRESUMO
Obesity and insulin resistance are independent risk factors for metabolic syndrome, diabetes, and cardiovascular disease. Adipose tissue samples from nonobese (NO), insulin-sensitive obese (ISO), and insulin-resistant obese (IRO) subjects from subcutaneous (SC) and omental (OM) adipose tissue (n = 28) were analyzed by microarray and confirmed by real-time PCR. Insulin signaling gene expression changes were greater in OM than in SC tissue and were related to insulin resistance rather than to obesity; few genes correlated with body mass index. Insulin receptor and insulin receptor substrate 1 (IRS-1) increased in the IRO versus pooled insulin-sensitive (NO+ISO) subjects. In glucose transport, PI3Kalpha and PDK2 decreased in IRO subjects, whereas PI3Kgamma, Akt2, GLUT4, and GLUT1 increased. IRS-1 regulators Jnk and IKK increased in IRO (P < 0.01 and P < 0.001 respectively). In protein synthesis, most genes examined were downregulated in IRO subjects, including mTor, Rheb, and 4EBP and eIF members (all P < 0.05). In proliferation, SHC, SOS, and Raf1 (P < 0.05) were increased, whereas Ras and MEK1/2 kinase 1 (P < 0.05) were decreased, in IRO subjects. Finally, in differentiation, PPARgamma, CEBPalpha, and CEBPbeta decreased, whereas PPARdelta, CEBPgamma, and CEBPepsilon increased, in IRO subjects (P < 0.05). Together, microarray and real-time PCR data demonstrate that insulin resistance rather than obesity is associated with altered gene expression of insulin signaling genes, especially in OM adipose tissue.
Assuntos
Regulação da Expressão Gênica/fisiologia , Resistência à Insulina/genética , Insulina/genética , Obesidade/metabolismo , Omento/metabolismo , Transdução de Sinais/genética , Gordura Subcutânea/metabolismo , Adulto , Feminino , Perfilação da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/fisiopatologia , Análise de Sequência com Séries de Oligonucleotídeos , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
AIM: The novel adipokine visfatin has 'insulin-mimicking' effects and is increased in models of diet-induced obesity, but factors that regulate visfatin have not been fully elucidated. METHODS: In order to determine visfatin regulation in adipocyte development and metabolism, as well as in pathophysiological conditions related to metabolic syndrome, endogenous visfatin expression was measured in 3T3-L1 pre-adipocytes and adipocytes using real-time reverse transcriptase polymerase chain reaction (real-time RT-PCR). RESULTS: A marked increase in visfatin expression was observed during differentiation, with a 2.2-fold increase between preconfluent and 2-day confluent cells even before differentiation was initiated. A further 4.1-fold increase was induced from day 0 to day 9 of differentiation (overall ninefold). Overnight incubation with dexamethasone (10(-8) to 10(-2) M) increased visfatin expression in both pre-adipocytes (1.5- to 3.3-fold, p < 0.05) and adipocytes (1.9-fold, p < 0.01). All other treatments decreased visfatin expression. In pre-adipocytes, visfatin expression decreased by 23% at a concentration of 1 microM insulin, 15% at 1-15 nM T3, 15% at 10 nM-1 microM progesterone, 33-44% at 10 nM-1 microM testosterone, 50% with palmitate and 30% with oleate (p < 0.05 for all). In adipocytes, insulin had a much greater effect, decreasing visfatin by 77% at 100 nM (p < 0.01), whereas oleate and sex hormones did not affect visfatin expression. However, tumor necrosis factor alpha, which had no effect on pre-adipocytes, significantly decreased visfatin in adipocytes by 26% at 10 ng/ml (p < 0.05). Interestingly, the thiazolidinedione (TZD) rosiglitizone also decreased visfatin by 28% at a concentration of 1 microM (p < 0.01). CONCLUSION: In summary, while the mechanism of visfatin action remains to be elucidated, the clear effects of multiple hormones on visfatin expression support a physiological role.
Assuntos
Adipócitos/metabolismo , Dexametasona/farmacologia , Estrogênios/farmacologia , Hormônios Esteroides Gonadais/farmacologia , Insulina/farmacologia , Nicotinamida Fosforribosiltransferase/genética , Progesterona/farmacologia , Testosterona/farmacologia , Células 3T3-L1 , Adipócitos/efeitos dos fármacos , Animais , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Camundongos , RNA Mensageiro/genética , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
Acylation-stimulating protein (ASP) and interaction with its receptor C5L2 influences adipocyte metabolism. We examined insulin resistance and differentiation-mediated regulation of C5L2 and the mechanistic impact on both C5L2 cell-surface protein and ligand binding to the receptor. C5L2 mRNA increased 8.7-fold with differentiation in 3T3-L1 cells (p < 0.0001) by day 9. In preadipocytes, insulin and dexamethasone increased C5L2 mRNA (1 micromol/L insulin resulted in a 2.6-fold increase, p < 0.01; 10 nmol/L dexamethasone resulted in a 17.9-fold increase, p < 0.01) and C5L2 cell-surface protein (100 nmol insulin resulted in a 2.7-fold increase, p < 0.001; 10 nmol/L dexamethasone resulted in a 2.8-fold increase, p < 0.001). In adipocytes, 100 nmol/L insulin increased C5L2 mRNA and ASP binding (respectively, 1.3-fold, p < 0.01; and 2.4-fold, p < 0.05). Dexamethasone decreased ligand binding (-60%, p < 0.02) without changing mRNA. Tumor necrosis factor alpha decreased C5L2 mRNA (-88% in preadipocytes and -38% in adipocytes, p < 0.001), C5L2 cell-surface protein (-53% in preadipocytes, p < 0.0001), and ASP binding (-60% and -49% in, respectively, preadipocytes and adipocytes, p < 0.05). Conversely, 1 micromol/L and 10 nmol/L rosiglitazone increased, respectively, C5L2 mRNA (9.3-fold, p < 0.0001) and ASP binding (2.4-fold, p < 0.05). Thus, C5L2 mRNA increases with differentiation, insulin, and thiazolidinedione treatment, and decreases with tumor necrosis factor alpha, all of which results in functional changes in ASP-C5L2 response and may have implications for human metabolism.
Assuntos
Adipócitos/citologia , Diferenciação Celular/fisiologia , Complemento C3a/metabolismo , Resistência à Insulina/fisiologia , Fator de Necrose Tumoral alfa/metabolismo , Acilação , Adipócitos/efeitos dos fármacos , Adipócitos/fisiologia , Animais , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular , Dexametasona/farmacologia , Glucocorticoides/farmacologia , Hipoglicemiantes/farmacologia , Camundongos , Receptor da Anafilatoxina C5a , Receptores de Quimiocinas/metabolismo , Tiazolidinedionas/farmacologiaRESUMO
AIM: Dysregulation of the normal levels of ghrelin, leptin and adiponectin in young non-obese subjects could promote food intake, diabetes and cardiovascular disease in later stages of life. Little information is available on how plasmatic concentrations of these hormones may be influenced by eating habits and/or components of energy balance in a young population, which if known, could facilitate their voluntary regulation. METHODS: In this cross-sectional study we examined the predictors of fasting plasma ghrelin, adiponectin and leptin in a population of well-characterized young non-obese women (N = 63). Energy intake was assessed by 24-hour dietary recall, resting metabolic rate (RMR) by indirect calorimetry, physical activity energy expenditure (PAEE) by tri-axial accelerometer, physical fitness by VO(2 peak), and eating behaviors by self administrated questionnaire. RESULTS: Lower RMR and higher HDL-cholesterol were independent predictors of higher plasma ghrelin explaining 17.6% of its variation even after correcting for BMI. Higher total or central fat mass was the only predictor of higher plasma leptin, and no other variable added any power to the prediction equation. Finally, higher energy intake and waist circumference and lower PAEE predicted lower plasma adiponectin in young non-obese women, explaining 43% of the variation in its concentrations even after correcting for total or central fat mass. CONCLUSION: Components of the energy balance (ie: energy intake and/or expenditure) influence adiponectin and ghrelin circulating levels. That is, higher energy intake and lower physical activity independently predict lower adiponectin concentrations, whereas lower resting metabolic rate independently predicts higher ghrelin levels in young non-obese women. Prospective studies are needed to examine whether circulating concentrations of ghrelin and adiponectin can be voluntarily regulated by lifestyle interventions.
Assuntos
Adiponectina/sangue , Metabolismo Energético , Estilo de Vida , Hormônios Peptídicos/sangue , Adulto , Metabolismo Basal , Composição Corporal , Dieta , Ingestão de Energia , Exercício Físico , Jejum , Feminino , Grelina , Humanos , Fome , Aptidão Física , Valor Preditivo dos TestesRESUMO
IL-6-deficient (IL-6(-/-)) mice develop obesity at 6-7 months of age. To elucidate the mechanisms of this mature-onset obesity, global gene expression profiles of 3-month-old preobese IL-6(-/-) were compared with those of IL-6(+/+) mice using DNA arrays. Genes that were up-regulated in IL-6(-/-) mice included the factors transthyretin and properdin in white adipose tissue and adipsin in muscle. These factors have been shown to influence the formation of acylation-stimulating protein (ASP), a cleavage product of complement C3. ASP stimulates the synthesis of triacylglycerol in adipocytes, and ASP-deficient mice are resistant to diet-induced obesity. In line with the increases in transthyretin, properdin, and adipsin, ASP levels in serum were increased by 31-54% in IL-6(-/-) compared with IL-6(+/+) mice. Furthermore, IL-6 replacement treatment in IL-6(-/-) mice decreased ASP levels significantly by 25-60%. In conclusion, ASP levels are increased in preobese IL-6(-/-) mice. This increase may result in increased triacylglycerol formation and uptake in IL-6(-/-) adipocytes and thereby contribute to the development of obesity in IL-6(-/-) mice.
Assuntos
Complemento C3a/análise , Interleucina-6/fisiologia , Adipócitos/patologia , Tecido Adiposo/metabolismo , Animais , Peso Corporal , Complemento C3/metabolismo , Complemento C3a/metabolismo , Ácidos Graxos não Esterificados/sangue , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Análise de Sequência com Séries de Oligonucleotídeos , Pré-Albumina/genética , Properdina/genética , Triglicerídeos/biossínteseRESUMO
OBJECTIVE: The purpose of this study was to determine the relationships between adipocyte hormones acylation stimulating protein (ASP), adiponectin, complement C3 (C3) (ASP precursor) and insulin, C-reactive protein (CRP), lipid profiles and insulin resistance in lean vs obese type 2 diabetes subjects. SUBJECTS: Lean type 2 diabetes subjects (DL n = 27) vs obese type 2 diabetes subjects (DO n = 55) were compared to age-matched nondiabetic groups (Obese, OB n = 55 and control, CTL n = 50). RESULTS: The DO group demonstrated significant increases in plasma ASP and C3 with decreases in plasma adiponectin as compared to CTL. Interestingly, these increases in ASP and C3 were as high, or greater, in the DL group in spite of normal weight. By contrast adiponectin in the DL group was comparable to CTL, in spite of marked insulin resistance. C3 correlated with insulin, glucose and homeostasis model assessment of insulin resistance (HOMA-IR); ASP correlated with body mass index (BMI), glucose, insulin and plasma lipid parameters (non-esterified fatty acids (NEFA), triglyceride, cholesterol and apolipoprotein B). Adiponectin correlated with BMI, glucose, NEFA, triglyceride, high-density lipoprotein cholesterol and apolipoprotein A1 but not HOMA-IR, ASP or C3. CRP correlated only with HOMA-IR. CONCLUSION: Increased ASP and C3 are both associated with diabetes and related lipid factors but are not regulated coordinately. Adiponectin appears to be more closely related to body size (decreased in obese subjects) than insulin resistance in these subjects.
Assuntos
Adiponectina/sangue , Complemento C3/análise , Complemento C3a/análise , Diabetes Mellitus Tipo 2/sangue , Obesidade/sangue , Adulto , Glicemia/metabolismo , Índice de Massa Corporal , Proteína C-Reativa/análise , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/fisiopatologia , Feminino , Humanos , Resistência à Insulina , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Obesidade/complicações , Obesidade/fisiopatologiaRESUMO
INTRODUCTION: Acylation-stimulating protein (ASP) is an adipocyte-derived protein that contributes to fatty acid clearance. Regular exercise training improves fatty acid handling. OBJECTIVE: To examine the effect of acute exercise and short-term endurance training on ASP levels. SUBJECTS: Eight untrained men (age: 23.5+/-3.4 y; maximal power output (Wmax): 3.7+/-0.6 W/kg body weight). DESIGN: Subjects were trained for 2 weeks. Before and after training, blood was sampled during a 3-h exercise test, and insulin sensitivity was assessed by an insulin tolerance test. RESULTS: Before training, ASP levels decreased during exercise (from 17.9+/-2.9 to 15.5+/-3.7 nmol/l at t=0 vs 180, P<0.05). Endurance training decreased fasting ASP levels significantly (17.9+/-2.9 vs 13.4+/-2.3 nmol/l pre- and post-training, P<0.001). Interestingly, after 2 weeks of endurance training, ASP levels tended to increase during exercise (from 13.4+/-2.3 to 17.2+/-4.5 nmol/l at t=0 vs 180, P=0.09). Baseline ASP levels correlated negatively with insulin sensitivity both before (r=-0.86, P<0.01) and after training (r=-0.82, P<0.05). CONCLUSION: Short-term endurance training reduces baseline ASP levels. These data fit with the hypothesis that reduced ASP levels indicate improved ASP sensitivity.