RESUMO
BACKGROUND: Adiponectin expression and plasma concentrations are decreased in human and animal models of obesity. Several single nucleotide polymorphisms (SNPs) in the adiponectin gene are known to influence the plasmatic concentration of the encoded protein. Some of these adiponectin polymorphisms have been associated with BMI in cross-sectional studies. OBJECTIVE: The aim of our study was to examine the longitudinal relationships between adiponectin gene polymorphisms and anthropometric indices. DESIGN: Two adiponectin gene (ADIPOQ) SNPs, -11391G>A and -11377C>G, were genotyped in 837 French Caucasian subjects from the SUpplémentation en VItamines et Minéraux Anti-oXydants (SU.VI.MAX) cohort. Anthropometric scores were measured at three clinical examinations over a 7-year period. RESULTS: For -11391G>A as well as for -11377C>G, we detected no association between the variant allele and anthropometric measurements at baseline. Considering longitudinal effects, we detected moderately higher waist-to-hip ratio (WHR) changes for the carriers of the -11391A (P=0.02) and -11377C (P=0.03) allele over the follow-up of the study. -11391G>A and -11377C>G define haplotypes associated also with WHR measurements and their changes over the follow-up of the study. Diploid configurations that combine -11391A and -11377C were associated with significantly higher WHR changes (DeltaCE: P=0.02) compared to other haplotypes. In addition, higher adiponectin levels were observed in AC/AC diplotypes compared to GG/GG carriers (P<0.0001). CONCLUSION: In the SU.VI.MAX study, genetic variations in the adiponectin gene affect abdominal fat gain over life span.
Assuntos
Adiponectina/genética , Polimorfismo de Nucleotídeo Único , Regiões Promotoras Genéticas/genética , Relação Cintura-Quadril , Adiponectina/sangue , Idoso , Antropometria/métodos , Índice de Massa Corporal , Feminino , Seguimentos , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/sangue , Obesidade/genética , Estudos ProspectivosRESUMO
AIMS/HYPOTHESIS: Dietary supplementation with conjugated linoleic acids (CLA) has a fat-reducing effect in various species, but induces severe hyperinsulinaemia and hepatic steatosis in the mouse. This study aimed to determine the causes of the deleterious effects of CLA on insulin homeostasis. METHODS: The chronology of adipose and liver weight, hepatic triglyceride accumulation and selected blood parameters, including lipids, insulin, leptin and adiponectin, was determined in C57BL/6J female mice fed a 1% isomeric mixture of CLA for various periods of time ranging from 2 to 28 days. Insulin secretion was measured in 1-h static incubations of pancreatic islets, and pancreas morphometric parameters were determined in mice fed CLA for 28 days. RESULTS: Plasma levels of leptin and adiponectin sharply decreased after 2 days of CLA feeding, although adipose tissue mass only decreased after day 6. Hyperinsulinaemia developed at day 6 and consistently worsened up to day 28, in parallel with increases in hepatic lipid content. Islets from CLA-fed mice displayed three- to four-fold increased rates of glucose-stimulated insulin secretion, both in the absence and presence of isobutyl methylxanthine or carbachol. The increased insulin-releasing capacity of islets from CLA-fed mice was explained by an increase in beta cell mass and number. CONCLUSIONS/INTERPRETATION: The data suggest that CLA supplementation induces a profound reduction of leptinaemia and adiponectinaemia, followed by hyperinsulinaemia due to the increased secretory capacity of pancreatic islets, leading, in turn, to liver steatosis. These observations cast doubt on the safety of dietary supplements containing CLA.
Assuntos
Hiperinsulinismo/induzido quimicamente , Peptídeos e Proteínas de Sinalização Intercelular/sangue , Ilhotas Pancreáticas/patologia , Leptina/sangue , Ácidos Linoleicos Conjugados/efeitos adversos , Adiponectina , Tecido Adiposo/anatomia & histologia , Animais , Peso Corporal , Modelos Animais de Doenças , Feminino , Hiperplasia , Insulina/metabolismo , Secreção de Insulina , Ilhotas Pancreáticas/metabolismo , Fígado/anatomia & histologia , Fígado/efeitos dos fármacos , Fígado/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Tamanho do Órgão , Triglicerídeos/metabolismoRESUMO
Conjugated linoleic acids (CLA) are positional and geometric dienoic isomers of linoleic acid. Dietary CLA supplementation leads to a drop in fat mass in various species, including in humans. The t10,c12-CLA isomer is responsible for this anti-obesity effect. The reduction of fat mass is especially dramatic in the mouse, in which it is associated with severe hyperinsulinemia, insulin resistance and massive liver steatosis. The origin of these adverse side effects and putative chronology of events leading to CLA-mediated lipoatrophic syndrome are presented and discussed in this review.
Assuntos
Diabetes Mellitus Lipoatrófica/etiologia , Gorduras na Dieta/farmacologia , Ácidos Linoleicos Conjugados/fisiologia , Tecido Adiposo/efeitos dos fármacos , Animais , Modelos Animais de Doenças , Fígado Gorduroso/induzido quimicamente , Resistência à Insulina/fisiologia , Ilhotas Pancreáticas/efeitos dos fármacos , Ácidos Linoleicos Conjugados/farmacologia , CamundongosRESUMO
The goal of this study was to compare the short-term effects of dietary n-3 polyunsaturated (fish oil) and monounsaturated (olive oil) fatty acids on glucose transport, plasma glucose and lipid controls in a dietary insulin resistance model using sucrose-fed rats. The underlying cellular and molecular mechanisms were also determined in the muscle and adipose tissue. Male Sprague-Dawley rats (5 weeks old) were randomized for diets containing 57.5 % (w/w) sucrose and 14 % lipids as either fish oil (SF), olive oil (SO) or a mixture of standard oils (SC) for 3 weeks. A fourth control group (C) was fed a diet containing 57.5 % starch and 14 % standard oils. After three weeks on the diet, body weight was comparable in the four groups. The sucrose-fed rats were hyperglycemic and hyperinsulinemic in response to glucose load. The presence of fish oil in the sucrose diet prevented sucrose-induced hyperinsulinemia and hypertriglyceridemia, but had no effect on plasma glucose levels. Insulin-stimulated glucose transport in adipocytes increased after feeding with fish oil (p < 0.005). These modifications were associated with increased Glut-4 protein (p < 0.05) and mRNA levels in adipocytes. In the muscle, no effect was found on Glut-4 protein levels. Olive oil, however, could not bring about any improvement in plasma insulin, plasma lipids or Glut-4 protein levels. We therefore conclude that the presence of fish oil, in contrast to olive oil, prevents insulin resistance and hypertriglyceridemia in rats on a sucrose diet, and restores Glut-4 protein quantity in adipocytes but not in muscle at basal levels. Dietary regulation of Glut-4 proteins appears to be tissue specific and might depend on insulin stimulation and/or duration of dietary interventions.
Assuntos
Adipócitos/metabolismo , Ácidos Graxos Monoinsaturados/farmacologia , Ácidos Graxos Insaturados/farmacologia , Glucose/metabolismo , Proteínas de Transporte de Monossacarídeos/metabolismo , Proteínas Musculares , Músculo Esquelético/metabolismo , Sacarose/farmacologia , Adipócitos/efeitos dos fármacos , Adipócitos/ultraestrutura , Animais , Transporte Biológico Ativo/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Separação Celular , Dieta , Ingestão de Alimentos , Teste de Tolerância a Glucose , Transportador de Glucose Tipo 4 , Técnicas In Vitro , Masculino , Proteínas de Transporte de Monossacarídeos/biossíntese , Músculo Esquelético/efeitos dos fármacos , Azeite de Oliva , Tamanho do Órgão/efeitos dos fármacos , Óleos de Plantas/farmacologia , RNA Mensageiro/biossíntese , Ratos , Ratos Sprague-DawleyRESUMO
The response of plasma leptin to a high-glycemic index (high-GI) starch diet after a short (3 weeks) and prolonged (12 weeks) period was determined in Sprague-Dawley rats. Age-matched rats were fed an identical isocaloric diet except that the carbohydrates were from either mung bean starch (low-GI) or waxy cornstarch (high-GI). After a single test meal of the high-GI starch diet, postprandial plasma glucose (P < .05) and insulin (P < .01) peaks and plasma glucose (P < .014) and insulin (P < .05) areas were higher versus the low-GI starch diet (n = 8 per group). Other age-matched control rats were fed the same diets for a longer period. After 3 weeks, ob mRNA levels were decreased by 50% (P < .005) in the epididymal adipose tissue of high-GI-fed rats versus low-GI-fed rats, without a significant decrease in plasma leptin. After 12 weeks of the high-GI starch diet, both plasma leptin and ob mRNA were decreased by 34% (P < .005) and 41% (P < .05), respectively, compared with the low-GI diet. Both relative epididymal adipose tissue weight (adjusted per 100 g body weight) and total fat mass, as measured by dual-energy x-ray absorptiometry (DEXA), were unchanged by the high-GI starch diet. Basal nonfasting plasma insulin, glucose, and triglycerides were not altered by the high-GI starch diet, whereas free fatty acids were significantly elevated and associated with a trend (P < .13) for increased plasma free glycerol. Plasma leptin levels were negatively correlated with free fatty acid levels (r = .56, P < .05). Despite low leptin, rats fed on the high-GI diet did not increase their food intake, suggesting increased leptin sensitivity. These findings might precede weight gain and the increase in fat mass. Chronic nutritional factors might alter plasma leptin via several overlapping factors independently of energy intake.
Assuntos
Carboidratos da Dieta/farmacologia , Leptina/sangue , Amido/farmacologia , Tecido Adiposo/metabolismo , Animais , Glicemia/análise , Composição Corporal , Peso Corporal , Ingestão de Alimentos , Fabaceae , Insulina/sangue , Leptina/genética , Masculino , Plantas Medicinais , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Amido/metabolismo , Triglicerídeos/sangueRESUMO
The of this study was to evaluate the chronic effects of a high (waxy corn) vs. a low (mung beans) glycemic index starch diet on the lipogenic enzymes, fatty acid synthase (FAS) and lipoprotein lipase (LPL). Normal and diabetic (streptozotocin-injected on d 2 of life) male Sprague-Dawley rats consumed a diet containing 575 g/kg carbohydrates either as waxy cornstarch (WCS) or as mung bean starch (MBS). After 3 wk, neither body weights nor relative epididymal fat pad weights differed. In diabetic rats, the WCS diet induced high basal plasma insulin levels. Plasma triglycerides were not significantly affected by diet in either normal or diabetic rats. Adipose tissue and liver LPL activities were not modified by the type of starch in the diet. In normal rats, FAS activity and gene expression in epididymal adipose tissue but not in liver were greater in rats consuming the WCS diet than in those consuming MBS. To evaluate the implication of insulin in this regulation, two genes regulated by insulin [GLUT4 and phosphoenolpyruvate carboxykinase (PEPCK)] were also studied. The high glycemic index WCS diet compared with the low glycemic index MBS diet resulted in lower hepatic PEPCK mRNA in both normal and diabetic rats. Normal, but not diabetic rats fed WCS had greater GLUT4 gene expression in adipocytes than did those fed MBS. We conclude that the total replacement of 575 g/kg low glycemic index starch by a high glycemic index starch for 3 wk caused the following in normal rats: 1) high FAS activity and mRNA in adipose tissue but not in liver and 2) high GLUT4 gene expression in adipose tissue. In both normal and diabetic rats this same diet resulted in lower hepatic PEPCK mRNA. Therefore, high glycemic index starch diet is implicated in stimulating FAS activity and lipogenesis and might have undesirable long-term metabolic effects.
Assuntos
Glicemia/metabolismo , Diabetes Mellitus Experimental/enzimologia , Carboidratos da Dieta/administração & dosagem , Ácido Graxo Sintases/metabolismo , Lipase Lipoproteica/metabolismo , Proteínas Musculares , Amido/administração & dosagem , Tecido Adiposo/anatomia & histologia , Tecido Adiposo/enzimologia , Animais , Epididimo , Fabaceae , Expressão Gênica , Transportador de Glucose Tipo 4 , Metabolismo dos Lipídeos , Fígado/enzimologia , Masculino , Proteínas de Transporte de Monossacarídeos/genética , Fosfoenolpiruvato Carboxiquinase (GTP)/genética , Plantas Medicinais , Ratos , Ratos Sprague-DawleyRESUMO
OBJECTIVE: To evaluate the effect of a moderate dose of fish oil on glycemic control and in vivo insulin action in type 2 diabetic men with elevated plasma triacylglycerols and to determine the effect of the same treatment on gene expression of GLUT4, lipoprotein lipase (LPL), and hormone-sensitive lipase (HSL) in the abdominal adipose tissue. RESEARCH DESIGN AND METHODS: A total of 12 type 2 diabetic men were randomly allocated to 2 months of 6 g daily of either fish oil or sunflower oil, separated by a 2-month washout interval, in a double-blind crossover design. RESULTS: For glucose metabolism, 2 months of fish oil supplementation compared with sunflower oil led to similar fasting plasma insulin, glucose, and HbA1c. Basal hepatic glucose production did not increase after fish oil. There was no difference in insulin suppression of hepatic glucose production nor in insulin stimulation of whole-body glucose disposal measured by the euglycemic-hyperinsulinemic clamp. Fish oil did not ameliorate the low mRNA level of GLUT4 in adipose tissue of these patients. For lipid profile, fish oil lowered plasma triacylglycerol more than sunflower oil (P < 0.05) and tended to increase the amount of mRNA of both LPL and HSL in adipose tissue. CONCLUSIONS: A moderate dose of fish oil did not lead to deleterious effects on glycemic control or whole-body insulin sensitivity in type 2 diabetic men, with preserved triacylglycerol-lowering capacities.