14 research outputs found
Body weight, metabolism and clock genes
Biological rhythms are present in the lives of almost all organisms ranging from plants to more evolved creatures. These oscillations allow the anticipation of many physiological and behavioral mechanisms thus enabling coordination of rhythms in a timely manner, adaption to environmental changes and more efficient organization of the cellular processes responsible for survival of both the individual and the species. Many components of energy homeostasis exhibit circadian rhythms, which are regulated by central (suprachiasmatic nucleus) and peripheral (located in other tissues) circadian clocks. Adipocyte plays an important role in the regulation of energy homeostasis, the signaling of satiety and cellular differentiation and proliferation. Also, the adipocyte circadian clock is probably involved in the control of many of these functions. Thus, circadian clocks are implicated in the control of energy balance, feeding behavior and consequently in the regulation of body weight. In this regard, alterations in clock genes and rhythms can interfere with the complex mechanism of metabolic and hormonal anticipation, contributing to multifactorial diseases such as obesity and diabetes. The aim of this review was to define circadian clocks by describing their functioning and role in the whole body and in adipocyte metabolism, as well as their influence on body weight control and the development of obesity
Allelic variations in the CYBA gene of NADPH oxidase and risk of kidney complications in patients with type 1 diabetes
International audienc
Glutathione peroxidase-1 gene (GPX1) variants, oxidative stress and risk of kidney complications in people with type 1 diabetes
International audienc
Weight-based combination therapy with peginterferon alpha-2b and ribavirin for NaĂŻve, relapser and non-responder patients with chronic hepatitis C
Combination therapy with pegylated interferon and ribavirin is considered the new standard therapy for naĂŻve patients with chronic hepatitis C. We evaluated the efficacy and safety of treatment with weight-based peginterferon alpha-2b (1.5 mg/kg per week) plus ribavirin (800-1,200 mg/day) for 48 weeks in naĂŻve, relapser and non-responder (to previous treatment with interferon plus ribavirin) patients with chronic hepatitis C. Sixty-seven naĂŻve, 26 relapser and 40 non-responder patients were enrolled. The overall sustained virological response (SVR) for the intention-to-treat population was 54% for naĂŻve, 62% for relapser and 38% for non-responder patients. In the naĂŻve subgroup, SVR was significantly higher in patients with the non-1 genotype (67%) compared to those with genotype 1 (45%). In relapsers and non-responders, SVR was, respectively, 69% and 24% in patients with genotype 1 and 43% and 73% in those with genotype non-1. There were no significant differences in SVR rates among the three body weight ranges (< 65 kg, 65-85 kg and > 85 kg) in any of the subgroups. Early virological response (EVR) was reached by 78%, 81% and 58% of naĂŻve, relapser and non-responder patients, respectively, and among those with EVR, 63%, 67% and 61%, respectively, subsequently achieved SVR. All of the non-responder patients who did not have EVR reached SVR. Treatment was discontinued in 13% of the patients, due to loss to follow-up, hematological abnormalities or depression
A role for mammalian target of rapamycin -mTOR- pathway in non alcoholic steatohepatitis related-cirrhosis
Summary. Non-alcoholic fatty liver disease (NAFLD)
encompasses the whole spectrum of steatosis, nonalcoholic
steatohepatitis (NASH), and NASH-related
cirrhosis (NASH/Cir). Although molecular advances
have been made in this field, the pathogenesis of
NAFLD is not completely understood. The gene
expression profiling associated to NASH/Cir was
assessed, in an attempt to better characterize the
pathways involved in its etiopathogenesis. Methods: In
the first step, we used cDNA microarray to evaluate the
gene expression profiles in normal liver (n=3) and
NASH/Cir samples (n=3) by GeneSifterâą analysis to
identify differentially expressed genes and biological
pathways. Second, tissue microarray was used to
determine immunohistochemical expression of
phosphorylated mTOR and 4E-BP1 in 11 normal liver
samples, 10 NASH/Cir samples and in 37 samples of
cirrhosis of other etiologies to further explore the
involvement of the mTOR pathway evidenced by the
gene expression analysis. Results: 138 and 106 genes
were, respectively, up and down regulated in NASH/Cir
in comparison to normal liver. Among the 9 pathways
identified as significantly modulated in NASH/Cir, the
participation of the mTOR pathway was confirmed,
since expression of cytoplasmic and membrane phosphomTOR
were higher in NASH/Cir in comparison to
cirrhosis of other etiologies and to normal liver.
Conclusions: Recent findings have suggested a role for
the cellular ânutrient sensorâ mTOR in NAFLD and the
present study corroborates the participation of this
pathway in NASH/Cir. Phospho-mTOR evaluation
might be of clinical utility as a potential marker for
identification of NASH/Cir in cases mistakenly
considered as cryptogenic cirrhosis owing to paucity of
clinical data
Linkage Disequilibrium With Hla-drb1-dqb1 Haplotypes Explains The Association Of Tnf-308g>a Variant With Type 1 Diabetes In A Brazilian Cohort.
A functional variant in the promoter region of the gene encoding tumor necrosis factor (TNF; rs1800629, -308G>A) showed to confer susceptibility to T1D. However, TNF rs1800629 was found, in several populations, to be in linkage disequilibrium with HLA susceptibility haplotypes to T1D. We evaluated the association of TNF rs1800629 with T1D in a cohort of Brazilian subjects, and assessed the impact of HLA susceptibility haplotypes in this association. 659 subjects with T1D and 539 control subjects were genotyped for TNF-308G>A variant. HLA-DRB1 and HLA-DQB1 genes were genotyped in a subset of 313 subjects with T1D and 139 control subjects. Associations with T1D were observed for the A-allele of rs1800629 (OR 1.69, 95% CI 1.33-2.15, p<0.0001, in a codominant model) and for 3 HLA haplotypes: DRB1*03:01-DQB1*02:01 (OR 5.37, 95% CI 3.23-8.59, p<0.0001), DRB1*04:01-DQB1*03:02 (OR 2.95, 95% CI 1.21-7.21, p=0.01) and DRB1*04:02-DQB1*03:02 (OR 2.14, 95% CI 1.02-4.50, p=0.04). Linkage disequilibrium was observed between TNF rs1800629 and HLA-DRB1 and HLA-DQB1 alleles. In a stepwise regression analysis HLA haplotypes, but not TNF rs1800629, remained independently associated with T1D. Our results do not support an independent effect of allelic variations of TNF in the genetic susceptibility to T1D.56850-5