Résumé
The morbidity and mortality of cardiovascular diseases (CVDs) are increasing worldwide and seriously threaten human life and health. Fibroblast growth factor 21 (FGF21), a metabolic regulator, regulates glucose and lipid metabolism and may exert beneficial effects on the cardiovascular system. In recent years, FGF21 has been found to act directly on the cardiovascular system and may be used as an early biomarker of CVDs. The present review highlights the recent progress in understanding the relationship between FGF21 and CVDs including coronary heart disease, myocardial ischemia, cardiomyopathy, and heart failure and also explores the related mechanism of the cardioprotective effect of FGF21. FGF21 plays an important role in the prediction, treatment, and improvement of prognosis in CVDs. This cardioprotective effect of FGF21 may be achieved by preventing endothelial dysfunction and lipid accumulating, inhibiting cardiomyocyte apoptosis and regulating the associated oxidative stress, inflammation and autophagy. In conclusion, FGF21 is a promising target for the treatment of CVDs, however, its clinical application requires further clarification of the precise role of FGF21 in CVDs.
Sujets)
Humains , Maladies cardiovasculaires , Facteurs de croissance fibroblastique , Métabolisme lipidique , Stress oxydatifRésumé
Overweight or obesity has become a serious public health problem in the world, scientists are concentrating their efforts on exploring novel ways to treat obesity. Nowadays, the availabilities of bariatric surgery and pharmacotherapy have enhanced obesity treatment, but it should has support from diet, physical exercise and lifestyle modification, especially the functional food. Resistant starch, an indigestible starch, has been studied for years for its beneficial effects on regulating blood glucose level and lipid metabolism. The aim of this review is to summarize the effect of resistant starch on weight loss and the possible mechanisms. According to numerous previous studies it could be concluded that resistant starch can reduce fat accumulation, enhance insulin sensitivity, regulate blood glucose level and lipid metabolism. Recent investigations have focused on the possible associations between resistant starch and incretins as well as gut microbiota. Resistant starch seems to be a promising dietary fiber for the prevention or treatment of obesity and its related diseases.
Sujets)
Hydrates de carbone alimentaires , Métabolisme , Fibre alimentaire , Métabolisme , Utilisations thérapeutiques , Tube digestif , Microbiologie , Physiologie , Microbiote , Obésité , Diétothérapie , Amidon , Métabolisme , Perte de poidsRésumé
<p><b>OBJECTIVE</b>To investigate the relationship of liver enzymes with hyperglycemia in a large population in Shanghai and identify the association between liver enzymes and insulin resistance.</p><p><b>METHODS</b>A total of 3 756 participants were enrolled. Each participant underwent an oral glucose tolerance test and completed a questionnaire. Anthropometric indices were recorded and serum samples were collected for measurement.</p><p><b>RESULTS</b>Liver enzymes concentrations were independently associated with i-IGT, IFG+IGT, and diabetes. With the increase of ALT and GGT concentrations, ORs for i-IGT, IFG+IGT, and diabetes increased gradually. By comparing patients in the highest quartile of GGT concentrations or ALT concentrations with those in the lowest quartile (Q1), ORs for i-IGT, IFG+IGT, or diabetes was significant after adjustment. Both ALT and GGT concentrations were linearly correlated with HOMA-IR and independently associated with HOMA-IR [ALT OR (95% CI): 2.56 (1.51-4.34) P=0.00; GGT OR (95% CI): 2.66 (1.53-4.65) P=0.00].</p><p><b>CONCLUSION</b>Serum ALT and GGT concentrations were closely related to pre-diabetes and diabetes in the Shanghai population and positively associated with insulin resistance.</p>
Sujets)
Adolescent , Adulte , Sujet âgé , Femelle , Humains , Mâle , Adulte d'âge moyen , Jeune adulte , Alanine transaminase , Sang , Anthropométrie , Chine , Hémoglobine glyquée , Métabolisme , Métabolisme lipidique , Foie , État prédiabétique , Sang , gamma-Glutamyltransferase , SangRésumé
<p><b>OBJECTIVE</b>To investigate how F261S mutation identified from Chinese obese patients affects the function of melanocortin 4 receptor (MC4R) and to analyze the obesity-related phenotypes in subjects carrying the F261S mutation.</p><p><b>METHODS</b>F261S mutant of MC4R was generated by site-directed mutagenesis. Plasmids encoding wild-type or F261S mutant of MC4R were transfected into HEK293 and COS-7 cells to examine their functional characteristics. Signaling properties of F261S MC4R were assessed by measuring intracellular cAMP levels in response to alpha-MSH stimulation. Cell surface expression of F261S MC4R was compared with that of wild-type MC4R. Clinical examinations were performed in subjects carrying F261S mutation and in non-mutated controls.</p><p><b>RESULTS</b>The alpha-MSH-stimulated reporter gene activity was significantly reduced in cells expressing F261S MC4R, with a maximal response equal to 57% of wild-type MC4R. The F261S mutation also led to a significant change in the Es50 value compared with the wild-type receptor (P<0.01). Immunofluorescent assay revealed a marked reduction in plasma membrane localization of the MC4R in cells expressing the F261S mutant receptor. The resting metabolic rate and fat composition of the mutant carriers were not significantly different from those of the non-mutated obese controls.</p><p><b>CONCLUSIONS</b>The decreased response to alpha-MSH due to the intracellular retention of MC4R may cause early-onset obesity in the F261S pedigree of Chinese.</p>
Sujets)
Adulte , Sujet âgé , Animaux , Enfant , Femelle , Humains , Mâle , Adulte d'âge moyen , Âge de début , Cellules COS , Chlorocebus aethiops , Chine , Mutation , Obésité , Épidémiologie , Métabolisme , Pedigree , Récepteur de la mélanocortine de type 4 , Génétique , MétabolismeRésumé
<p><b>OBJECTIVE</b>To analyze the association of variants of hepatocyte nuclear factor-1alpha (HNF-1alpha) gene with type 2 diabetes in Chinese population.</p><p><b>METHODS</b>In 152 unrelated type 2 diabetes patients and 93 unrelated controls, eleven single nucleotide polymorphisms (SNPs) were identified and genotyped. Statistical analyses were performed to investigate whether these SNPs were associated with diabetes status in our samples.</p><p><b>RESULTS</b>In the individual SNP study, no SNP differed significantly in frequency between type 2 diabetes patients and controls. In the haplotype analysis, two haplotype blocks were identified. In haplotype block 1, no evidence was found between common HNF-1alpha haplotypes and type 2 diabetes. However, in haplotype block 2, a common haplotype GCGC formed by four tagging SNPs (tSNPs) was found to be associated with decreased risk of type 2 diabetes (odds ratio [OR] 0.6011, 95% confidence interval [CI] 0.4138-0.8732, P = 0.0073, empirical P = 0.0511, permutation test). A similar trend was also observed in the diplotype analysis, indicating that the increasing copy number of the haplotype GCGC was associated with the decreased frequency of diabetes (P = 0.0193).</p><p><b>CONCLUSION</b>The results of this study provide evidence that the haplotype of HNF-1alpha decreases the risk of type 2 diabetes in Chinese individuals.</p>
Sujets)
Adulte , Sujet âgé , Humains , Adulte d'âge moyen , Études cas-témoins , Chine , Épidémiologie , Diabète de type 2 , Épidémiologie , Génétique , Prédisposition génétique à une maladie , Haplotypes , Facteur nucléaire hépatocytaire HNF-1 alpha , Génétique , Polymorphisme de nucléotide simpleRésumé
<p><b>OBJECTIVE</b>To apply linkage disequilibrium (LD) maps to associations studies with high throughput single nucleotide polymorphisms (SNPs).</p><p><b>METHODS</b>Seven hundred and fifty-four SNPs were genotyped in 160 Shanghai Chinese. LD maps were constructed in cases and controls separately. By comparing the decline of LD unit with distance between the two groups, disease susceptible loci were estimated. This method was compared with traditional analyses including LD analysis, single SNP and haplotype analyses.</p><p><b>RESULTS</b>The analysis of LD maps could detect the chromosome regions with different LD patterns between the cases and controls. The alleles and/or haplotypes frequencies of SNPs within the regions had significantly different distributions or trends of significantly different distributions.</p><p><b>CONCLUSION</b>This method may be applied to analyze the data from association studies with high throughput SNPs genotype information.</p>
Sujets)
Adulte , Sujet âgé , Femelle , Humains , Mâle , Études cas-témoins , Protéines de liaison à l'ADN , Génétique , Diabète de type 2 , Génétique , Fréquence d'allèle , Étude d'association pangénomique , Méthodes , Haplotypes , Déséquilibre de liaison , Polymorphisme de nucléotide simple , Facteur de transcription-1 de la leucémie pré-B , Protéines proto-oncogènes , Génétique , Récepteur X des rétinoïdes type gamma , GénétiqueRésumé
<p><b>OBJECTIVE</b>To investigate the relationship between adiponectin receptor 1 gene (ADIPOR1) single nucleotide polymorphism (SNP) and glucose metabolism and insulin resistance in the Chinese.</p><p><b>METHODS</b>The genotypes of -3881T/C of ADIPOR1 were determined through polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP) in 664 Chinese in Shanghai. Among them, 370 were subjects with normal glucose tolerance and 294 were newly diagnosed diabetic patients without taking any drug. Phenotype measured were: height, weight to calculate body mass index; systolic blood pressure and diastolic blood pressure; plasma glucose level, serum insulin and C-peptide levels of blood obtained both at 0 and 120 minute during a standard 75-gram glucose oral glucose tolerance test. Insulin resistance and beta cell function were assessed by homeostasis model assessment (HOMA-IR and HOMA-B).</p><p><b>RESULTS</b>(1) The frequencies of two alleles did not differ between the type 2 diabetic patients and ones with normal glucose tolerance (P is 0.6749). (2) The frequency of C allele is significantly lower in type 2 diabetic patients with insulin resistance compare with those without insulin resistance (P is 0.0121). (3) In type 2 diabetic patients, the C allele carriers had a significantly lower diastolic blood pressure (P is 0.0466) and HOMA-IR (P is 0.0498). (4) In subjects with normal glucose tolerance, the C allele carriers had a significantly lower fasting plasma glucose (P is 0.0140).</p><p><b>CONCLUSION</b>These findings suggest that variant of ADIPOR1 plays a role in glucose metabolism and insulin resistance in the Chinese.</p>
Sujets)
Sujet âgé , Femelle , Humains , Mâle , Adulte d'âge moyen , Allèles , Asiatiques , Génétique , Chine , Fréquence d'allèle , Génotype , Glucose , Métabolisme , Insulinorésistance , Génétique , Réaction de polymérisation en chaîne , Polymorphisme de restriction , Polymorphisme de nucléotide simple , Génétique , Récepteurs à l'adiponectine , GénétiqueRésumé
<p><b>OBJECTIVE</b>To screen the mutation of hepatocyte nuclear factor 4 alpha gene (HNF4A) in Chinese pedigrees with early and/or multiplex-onset diabetes in Shanghai and nearby area.</p><p><b>METHODS</b>By PCR-single strand conformation polymorphism (PCR-SSCP) and direct sequencing, the mutation screen of HNF4A gene was performed in 93 normal controls and 154 unrelated probands from early- and/or multiplex-onset diabetes. The PCR-RFLP was used to analyze the frequencies of the discovered mutations and variants.</p><p><b>RESULTS</b>Two synonymous mutations (N153N, A158A) were found in two families, of which the N153N was co-segregated with early-onset diabetes. These two synonymous mutations were not detected in the 93 normal controls. Three variants, IVS1+308(A to G)(rs2071197), IVS1+357(A to T)(rs2071198), IVS1-5(C to T)(rs745975), were also identified in this study. The genotype and allele frequencies of the three variants had no difference between the probands and normal controls.</p><p><b>CONCLUSION</b>HNF4A gene mutation is rare in Chinese pedigrees with early and/or multiplex-onset diabetes.</p>
Sujets)
Adulte , Femelle , Humains , Mâle , Âge de début , Séquence nucléotidique , Chine , Épidémiologie , Diabète , Épidémiologie , Génétique , Fréquence d'allèle , Génotype , Facteur nucléaire hépatocytaire HNF-4 , Génétique , Mutation , Pedigree , Réaction de polymérisation en chaîne , Polymorphisme de conformation simple brin , Analyse de séquence d'ADNRésumé
<p><b>OBJECTIVE</b>To investigate the relationship of the C to T variant at the -55 site of the promoter region of uncoupling protein 3 gene (UCP3) with the resting energy expenditure and the parameters of body fat in Chinese population.</p><p><b>METHODS</b>Three hundred Chinese (91 normal weight subjects, 209 overweight/obesity subjects) were genotyped for the UCP3 gene -55(C>T) by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Resting energy expenditure (REE), fat mass (FM), fat free mass (FFM) and the parameters for regional adipose tissue distribution were measured.</p><p><b>RESULTS</b>Genotype frequencies of UCP3 gene -55(C>T) were not associated with obesity and different types of obesity. The REE level in normal weight subjects with TT homozygotes was higher than that in those with CT heterozygotes and CC homozygotes (P=0.0200). Similar tendency was also observed in overweight/obesity subjects. The FM/FFM exhibited significant difference between the overweight/obesity subjects with a TT genotype and those with a CT or CC genotype (P=0.0096).</p><p><b>CONCLUSION</b>The level of difference in REE caused by the polymorphism of promoter region of UCP3 -55(C>T) may play a role in energy metabolism in Chinese.</p>
Sujets)
Femelle , Humains , Mâle , Adulte d'âge moyen , Tissu adipeux , Métabolisme , Asiatiques , Génétique , Chine , Métabolisme énergétique , Physiologie , Canaux ioniques , Génétique , Physiologie , Protéines mitochondriales , Génétique , Physiologie , Réaction de polymérisation en chaîne , Polymorphisme de restriction , Polymorphisme de nucléotide simple , Protéine-3 de découplageRésumé
<p><b>OBJECTIVE</b>To investigate the prevalence of mutations of hepatocyte nuclear factor (HNF)-1 alpha gene in Chinese families with early-onset and/or multiplex diabetes mellitus.</p><p><b>METHODS</b>The studied population consisted of 247 unrelated Chinese residents in Shanghai, including 93 healthy controls and 154 probands of early-onset and/or multiplex diabetes pedigrees. The ten exons, flanking introns and minimal promoter region of HNF-1 alpha gene were screened using polymerase chain reaction-single strand conformation polymorphism and DNA sequencing.</p><p><b>RESULTS</b>Fourteen substitutions were identified in 154 probands. Three variants were not observed in 93 healthy controls. Two of them (nt-128T-->G IVS2 nt+21G-->A) were not reported previously and all co-segregated with diabetes. The genotype and allele frequencies of the other eleven variants in the diabetic patients were not significantly different from those in the healthy controls. There were no significant relationships between the eleven variants of HNF-1 alpha gene and clinical variables (plasma glucose, insulin, C-peptide and fasting lipid profile).</p><p><b>CONCLUSION</b>HNF-1 alpha gene is not a major cause of early-onset or multiplex diabetes pedigrees in this Chinese population in Shanghai.</p>