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Morphogens are intercellular signaling molecules providing spatial information to cells in developing tissues to coordinate cell fate decisions. The spatial information is encoded within long-ranged concentration gradients of the morphogen. Direct measurement of morphogen dynamics in a range of systems suggests that local and global diffusion coefficients can differ by orders of magnitude. Further, local diffusivity can be large, which would potentially abolish any concentration gradient rapidly. Such observations have led to alternative transport models being proposed, including transcytosis and cytonemes. Here, we show that accounting for tissue architecture combined with receptor binding is sufficient to hinder the diffusive dynamics of morphogens, leading to an order of magnitude decrease in the effective diffusion coefficient from local to global scales. In particular, we built a realistic in silico architecture of the extracellular spaces of the zebrafish brain using light and electron microscopy data. Simulations on realistic architectures demonstrate that tortuosity and receptor binding within these spaces are sufficient to reproduce experimentally measured morphogen dynamics. Importantly, this work demonstrates that hindered diffusion is a viable mechanism for gradient formation, without requiring additional regulatory control.
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BACKGROUND AND AIMS: High-sensitivity C-reactive protein (hs CRP) has emerged as an inflammatory biomarker to predict metabolic syndrome. Here, we investigate the association of hs CRP with metabolic variables and determine the risks for elevated hs CRP levels in healthy Singaporean adults. METHODS: We conducted a cross-sectional study of 225 participants (104 men). The levels of hs CRP and fasting lipid parameters were analyzed by COBAS. Body composition was determined with dual-energy X-ray absorptiometry. RESULTS: Twenty-one (9 %) participants had elevated hs CRP levels (>3 mg/mL). The levels of hs CRP had significant correlations (p <0.05) with obesity and metabolic variables among women. Stepwise multivariate regression analysis identified FM (%) (accounted for 22.5% of the variability in hs CRP levels) as a major determinant of hs CRP levels. On multivariate regression, FM (%) was the independent determinant of intermediate and elevated hs CRP in women after adjustment for the potential confounders. CONCLUSIONS: Obesity may play a direct role in the elevated hs CRP levels in women, but not men living in Singapore. This is probably due to different body composition or different effects of sex hormones on adipose tissue between men and women.
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Proteína C-Reativa/análise , Obesidade/sangue , Adulto , Composição Corporal , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Regressão , Fatores Sexuais , SingapuraRESUMO
BACKGROUND: Type 2 diabetes (T2D) is the leading cause of nephropathy in the United States. Renal complications of T2D include proteinuria and suboptimal serum 25-hydroxycholecalciferol (25D) concentrations. 25D is the major circulating form of vitamin D and renal reabsorption of the 25D-vitamin D-binding protein (DBP) complex via megalin-mediated endocytosis is believed to determine whether 25D can be activated to 1,25-dihydroxycholecalciferol (1,25D) or returned to circulation. We previously demonstrated that excessive urinary excretion of 25D-DBP and albuminuria occurred in rats with type 1 diabetes (T1D) and T2D. Moreover, feeding rats with T1D high-amylose maize partially resistant to digestion [resistant starch (RS)] prevented excretion of 25D-DBP without significantly affecting hyperglycemia. OBJECTIVE: We used Zucker diabetic fatty (ZDF) rats, a model of obesity-related T2D, to determine whether feeding RS could similarly prevent loss of vitamin D and maintain serum 25D concentrations. METHODS: Lean control Zucker rats (n = 8) were fed a standard semi-purified diet (AIN-93G) and ZDF rats were fed either the AIN-93G diet (n = 8) or the AIN-93G diet in which cornstarch was replaced with RS (550 g/kg diet; 35% resistant to digestion) (n = 8) for 6 wk. RESULTS: RS attenuated hyperglycemia by 41% (P < 0.01) and prevented urinary DBP excretion and albuminuria, which were elevated 3.0- (P < 0.01) and 3.6-fold (P < 0.01), respectively, in control diet-fed ZDF rats. Additionally, urinary excretion of 25D (P = 0.01) and 1,25D (P = 0.03) was higher (89% and 97%, respectively), whereas serum 25D concentrations were 31% lower (P < 0.001) in ZDF rats fed the control diet compared with RS-fed ZDF rats. Histopathologic scoring of the kidney revealed that RS attenuated diabetes-mediated damage by 21% (P = 0.12) despite an â¼50% decrease in megalin protein abundance. CONCLUSIONS: Taken together, these data provide evidence that suggests vitamin D balance can be maintained by dietary RS through nephroprotective actions in T2D, which are independent of vitamin D supplementation and renal expression of megalin.
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Ração Animal/análise , Calcifediol/sangue , Vitamina D/metabolismo , Animais , Carboidratos da Dieta/administração & dosagem , Digestão , Regulação da Expressão Gênica/fisiologia , Rim/metabolismo , Masculino , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Distribuição Aleatória , Ratos , Ratos Zucker , Vitamina D/urina , Zea mays/química , Zea mays/metabolismoRESUMO
A reduction in carbohydrate intake and low-carbohydrate diets are often advocated to prevent and manage diabetes. However, limiting or eliminating carbohydrates may not be a long-term sustainable and maintainable approach for everyone. Alternatively, diet strategies to modulate glycemia can focus on the glycemic index (GI) of foods and glycemic load (GL) of meals. To assess the effect of a reduction in glycemic load of a 24 h diet by incorporating innovative functional ingredients (ß-glucan, isomaltulose) and alternative low GI Asian staples (noodles, rice)on glycemic control and variability, twelve Chinese men (Age: 27.0 ± 5.1 years; BMI:21.6 ± 1.8kg/m2) followed two isocaloric, typically Asian, 24h diets with either a reduced glycemic load (LGL) or high glycemic load (HGL) in a randomized, single-blind, controlled, cross-over design. Test meals included breakfast, lunch, snack and dinner and the daily GL was reduced by 37% in the LGL diet. Continuous glucose monitoring provided 24 h glycemic excursion and variability parameters: incremental area under the curve (iAUC), max glucose concentration (Max), max glucose range, glucose standard deviation (SD), and mean amplitude of glycemic excursion (MAGE), time in range (TIR). Over 24h, the LGL diet resulted in a decrease in glucose Max (8.12 vs. 6.90 mmol/L; p = 0.0024), glucose range (3.78 vs. 2.21 mmol/L; p = 0.0005), glucose SD (0.78 vs. 0.43 mmol/L; p = 0.0002), mean amplitude of glycemic excursion (2.109 vs. 1.008; p < 0.0001), and increase in 4.5-6.5mmol/L TIR (82.2 vs. 94.6%; p = 0.009), compared to the HGL diet. The glucose iAUC, MAX, range and SD improved during the 2 h post-prandial window of each LGL meal, and this effect was more pronounced later in the day. The current results validate the dietary strategy of incorporating innovative functional ingredients (ß-glucan, isomaltulose) and replacing Asian staples with alternative low GI carbohydrate sources to reduce daily glycemic load to improve glycemic control and variability as a viable alternative to the reduction in carbohydrate intake alone. These observations provide substantial public health support to encourage the consumption of staples of low GI/GL to reduce glucose levels and glycemic variability. Furthermore, there is growing evidence that the role of chrononutrition, as reported in this paper, requires further examination and should be considered as an important addition to the understanding of glucose homeostasis variation throughout the day.
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Dieta , Carboidratos da Dieta/administração & dosagem , Controle Glicêmico , Adulto , Glicemia/análise , Estudos Cross-Over , Alimentos , Humanos , Isomaltose/administração & dosagem , Isomaltose/análogos & derivados , Masculino , Oryza , Método Simples-Cego , beta-Glucanas/administração & dosagemRESUMO
OBJECTIVES: Despite being secreted exclusively by adipocytes, circulating adiponectin (ApN) is negatively associated with obesity. Moreover, obesity is traditionally viewed as leading to increased bone mass and density. Therefore, ApN may play a biological role in regulating fat and bone metabolism. The objective of this study is to evaluate the relationship between ApN, measures of obesity, and bone mineral density (BMD) in healthy adults living in Singapore. METHODS: We conducted a cross-sectional study of 300 participants (112 men), and measured body composition (i.e., fat mass, fat-free mass, BMD, and bone mineral content) by dual-energy x-ray absorptiometry. Serum leptin and ApN levels were determined by radioimmunoassay. RESULTS: Our results showed that serum ApN levels were significantly associated with obesity measures in both men and women, and the greater effect was observed in men. In contrast, the relationship between ApN and BMD was sex-dependent. Levels of ApN were negatively associated with BMD in women, but not in men. This relationship persisted even after adjustment for potential confounding factors, such as leptin and body mass index. Moreover, serum ApN was found to be a major determinant of BMD in women on the multivariate regression analysis. CONCLUSIONS: Our results suggest that ApN, an adipocyte-derived hormone, may affect bone metabolism, which may be mediated by sex hormones.
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Adiponectina/sangue , Índice de Massa Corporal , Densidade Óssea , Obesidade/sangue , Caracteres Sexuais , Absorciometria de Fóton , Tecido Adiposo/metabolismo , Adulto , Idoso , Composição Corporal , Osso e Ossos/metabolismo , Estudos Transversais , Feminino , Humanos , Leptina/sangue , Masculino , Pessoa de Meia-Idade , Análise de Regressão , Adulto JovemRESUMO
OBJECTIVES: It has been demonstrated that leptin influences the energy balance by regulating appetite and increasing energy expenditure (EE). However, the relationship between circulating leptin and EE is confounded owing to variations in body composition. The aim of this study was to determine the role of circulating leptin in energy regulation and to examine whether the leptin-mediated changes in EE are associated with adiposity among healthy adults living in Singapore. METHODS: We conducted a cross-sectional study of 300 participants (112 men). Resting metabolic rate (RMR) was measured by indirect calorimetry. Body composition (i.e., fat mass [FM] and fat-free mass [FFM]) was measured by dual-energy x-ray absorptiometry. Serum leptin levels were determined by radioimmunoassay. RESULTS: There were strong correlations between circulating leptin levels, FM, and RMR in healthy men and women. After normalization of RMR by a power function model (kcal·kg FFM0.86·d-1), the influence of FFM can be effectively removed. The normalized RMR was significantly associated with both FM (râ¯=â¯0.28, P < 0.001) and log leptin (râ¯=â¯0.35, P < 0.001). In the stepwise multiple regression analysis, leptin level is the major predictor for normalized RMR, accounting for 12% of the variation. In contrast, FM did not explain any variation in normalized RMR. CONCLUSION: Leptin may be a more significant predictor of normalized RMR than FM per se. The contribution of FM to RMR could be via a mechanism that is related to leptin-dependent responses involved in energy homeostasis.
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Metabolismo Basal/fisiologia , Metabolismo Energético/fisiologia , Leptina/sangue , Absorciometria de Fóton , Adulto , Idoso , Composição Corporal , Índice de Massa Corporal , Calorimetria Indireta , Estudos Transversais , Feminino , Voluntários Saudáveis , Humanos , Masculino , Pessoa de Meia-Idade , Singapura , Adulto JovemRESUMO
OBJECTIVES: Regional fat accumulation may play an important role in the pathogenesis of metabolic syndrome (MetS) and cardiovascular diseases, yet the results are controversial. The aim of this study was to determine the relationship between regional fat accumulation and MetS as well as the underlying mechanism in Chinese adults. METHODS: We conducted a cross-sectional study of 428 Chinese adults (166 men and 262 women). Android and gynoid fat percentage (AFP and GFP) were measured by dual energy x-ray absorptiometry. Fasting lipid parameters were analyzed by chemistry analyzer COBAS. RESULTS: Forty-six (28%) men and 34 (13%) women had MetS according to the modified National Cholesterol Education Panel Adult Treatment Panel III definition for South Asia. AFP was strongly correlated with more metabolic risk factors than GFP in men. In women, AFP and GFP showed significant opposite effects on triacylglycerol, high-density lipoprotein cholesterol, and waist circumference. On multivariate regression, AFP was an independent determinant of MetS in men after adjustment for confounding factors. For women, both AFP and the homeostatic model assessment for insulin resistance were predictors for MetS. CONCLUSIONS: Increased android fat may play a direct role in the development of MetS in Chinese adults. However, the associations between android fat, insulin resistance, and MetS are sex-dependent. This is probably due to different effects of sex hormones on adipose tissue or by genetic factors between sexes. Knowing the sex differences in developing MetS may help design sex-specific preventive strategies that will benefit the overall population health.
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Tecido Adiposo/diagnóstico por imagem , Síndrome Metabólica/diagnóstico , Absorciometria de Fóton/métodos , Adulto , China , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores SexuaisRESUMO
OBJECTIVES: Insulin resistance (IR) is important in the pathogenesis of diabetes, the prevalence of which has become a major public health threat in Asia. The aim of this study was to use ultrasound measurements of abdominal fat thickness to predict IR and low high-density lipoprotein cholesterol (HDL-C) levels among Singaporean adults. METHODS: A total of 399 healthy Singaporeans (mean age 36.7 ± 14.3 y; 43.4% men) took part in this study. Preperitoneal fat thickness (PFT) and subcutaneous fat thickness (SFT) were determined by ultrasound. RESULT: We found that both PFT and SFT had significant positive correlations (P < 0.05) with fasting insulin concentration, homeostasis model assessment of insulin resistance, triacylglycerol (TG), and blood pressure, and negatively correlated to serum HDL-C in all participants. Separating men and women, PFT was an independent determinant of IR and low HDL-C only in men. On receiver-operating characteristic curve analysis, PFT ≥1.2 cm was the optimal cutoff value to identify IR and low HDL-C in men. On the other hand, SFT was the determinant of IR, elevated TG, and low HDL-C only in women. An SFT of 1.1 cm was the optimal cutoff value to define IR, elevated TG, and low HDL-C in women. CONCLUSIONS: Results of this study suggested that ultrasound measurements of PFT and SFT could provide simple and useful indices of IR and lipid disorders for healthy Singaporean men and women. They might have the diagnostic values for predicting cardiovascular risks in this population.
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Dislipidemias/etiologia , Resistência à Insulina/fisiologia , Gordura Intra-Abdominal/diagnóstico por imagem , Medição de Risco/métodos , Gordura Subcutânea Abdominal/diagnóstico por imagem , Ultrassonografia/estatística & dados numéricos , Adulto , HDL-Colesterol/sangue , Estudos Transversais , Jejum , Feminino , Voluntários Saudáveis , Humanos , Insulina/sangue , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Curva ROC , Valores de Referência , Fatores de Risco , Singapura , Triglicerídeos/sangue , Ultrassonografia/métodosRESUMO
Few studies have been conducted to measure body composition in Asian populations. In this study, we determined the percent body fat (PBF) by using dual-energy X-ray absorptiometry (DEXA), air-displacement plethysmography (ADP or BOD POD), bioelectrical impedance analysis (BIA) and skinfold (SKF) in 445 healthy Singaporean adults. We observed that the BOD POD, BIA and SKF estimates of PBF were highly correlated with that from DEXA (as a reference method) among Singaporean adults. However, they all underestimated PBF (differences of 3.9% for BOD POD, 5.6% for BIA and 12.5% for SKF). Our results filled a gap in the literature by testing the relationships between DEXA and BOD POD, BIA and SKF in a large sample with a wide range of body mass index (BMI) from 16.1 to 37.5 kg/m² and age from 21 to 69.2 years. The differences of PBF measured by different methods were dependent on age, gender and ethnicity. No significant difference was observed between DEXA and BOD POD in men aged > 40 or in BMI tertile 3. However, the mean difference between DEXA and BOD POD was significant in women. Different measuring methods of estimating PBF therefore must be cautiously interpreted.
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Absorciometria de Fóton , Adiposidade , Dobras Cutâneas , Adiposidade/etnologia , Adulto , Fatores Etários , Idoso , Povo Asiático , Estudos Transversais , Impedância Elétrica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pletismografia/métodos , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Fatores Sexuais , Singapura , Adulto JovemRESUMO
BACKGROUND: Obesity has long been highlighted for its association with increased incidence of cardiovascular disease (CVD). Nonetheless, the best adiposity indices to evaluate the CVD risk factors remain contentious and few studies have been performed in Asian populations. In the present study, we compared the association strength of percent body fat (PBF) to indirect anthropometric measures of general adiposity (body mass index (BMI) and body adiposity index (BAI)) and central adiposity (waist circumference (WC), and waist-to-hip ratio (WHR)) for the prediction of CVD risk factors in healthy men and women living in Singapore. METHODS: A total of 125 individuals (63 men and 62 women) took part in this study. PBF was measured by using three different techniques, including bioelectrical impedance analysis (BIA), BOD POD, and dual-energy X-ray absorptiometry (DEXA). Anthropometric measurements (WC, hip circumference (HC), height, and weight), fasting blood glucose (FBG), fasting serum insulin (FSI), and lipid profiles were determined according to standard protocols. Correlations of anthropometric measurements and PBF with CVD risk factors were compared. RESULTS: Irrespective of the measuring techniques, PBF showed strong positive correlations with FSI, HOMA-IR, TC/HDL, TG/HDL, and LDL/HDL in both genders. While PBF was highly correlated with FBG, SBP, and DBP in females, no significant relationships were observed in males. Amongst the five anthropometric measures of adiposity, BAI was the best predictor for CVD risk factors in female participants (r = 0.593 for HOMA-IR, r = 0.542 for TG/HDL, r = 0.474 for SBP, and r = 0.448 for DBP). For males, the combination of WC (r = 0.629 for HOMA-IR, and r = 0.446 for TG/HDL) and WHR (r = 0.352 for SBP, and r = 0.366 for DBP) had the best correlation with CVD risk factors. CONCLUSION: Measurement of PBF does not outperform the simple anthropometric measurements of obesity, i.e. BAI, WC, and WHR, in the prediction of CVD risk factors in healthy Asian adults. While measures of central adiposity (WC and WHR) tend to show stronger associations with CVD risk factors in males, measures of general adiposity (BAI) seems to be the best predictor in females. The gender differences in the association between adiposity indices and CVD risk factors may relate to different body fat distribution in males and females living in Singapore. These results may find further clinical utility to identify patients with CVD risk factors in a more efficient way.
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We previously demonstrated that feeding of dietary resistant starch (RS) prior to the induction of diabetes delayed the progression of diabetic nephropathy and maintained vitamin D balance in streptozotocin (STZ)-induced type 1 diabetic (T1D) rats. Here, we examined the impact of RS on kidney function and vitamin D homeostasis following STZ injection. Male Sprague-Dawley rats were administered STZ and fed a standard diet containing cornstarch or 20, 10, or 5% RS for 4 weeks. T1D rats fed 10 and 20% RS, but not 5% RS, gained more weight than cornstarch-fed rats. Yet, renal health and glucose metabolism were not improved by RS. Our data suggest that RS normalized growth patterns in T1D rats after diabetes induction in a dose-dependent manner despite having no effect on blood glucose and vitamin D balances. Future interventions should focus on the preventative strategies with RS in T1D.