Correlation of peroxisome proliferator-activated receptor (PPAR-γ) mRNA expression with Pro12Ala polymorphism in obesity.

Our study aimed to analyze whether the expression of PPARγ mRNA in subcutaneous adipocyte tissue correlates with Pro12Ala PPARγ2 polymorphism in the obesity context. We found that mRNA expression of PPARγ in subcutaneous adipose tissue was greater in obese subjects (P < 0.05) than in the nonobese control group. Concurrently, genotyping of the Pro12Ala polymorphism showed that obese subjects possess a significantly higher frequency of the Pro/Pro genotype than nonobese controls (90.5 vs 79.5%; P = 0.03), suggesting that this genotype is involved in an increased risk of obesity in the Tunisian population. Taken together, our results demonstrate that the Pro12 allele is accompanied by an overexpression of PPARγ mRNA in subcutaneous adipocyte tissue, suggesting that the PPARγ Pro12Ala variant may contribute to the observed variability in PPARγ mRNA expression and consequently in body mass index and insulin sensitivity in the general population.

Relationship of thyroid function with obesity and type 2 diabetes in euthyroid Tunisian subjects.

OBJECTIVES: Although a relationship between obesity and metabolic consequences with thyroid function has been reported, the underlying pathogenesis is not completely known. In the current study, we evaluated the thyroid function in obese and/or diabetic patients compared to healthy normal weight peers, exploring the possible association between components of metabolic syndrome and thyroid function parameters. METHODS: We recruited 108 subjects (56 male and 52 female). In all subjects, thyroid stimulating hormone (TSH), free thyroxine (FT4), fasting plasma levels of insulin and glucose, homeostasis model assessment for insulin resistance, and obesity parameters were assessed. RESULTS: We found that circulating levels of TSH and FT4 were significantly increased in overweight and obese subjects. However, the data do not reveal any change of these hormones in diabetics. Multivariate linear regression analysis showed that TSH was directly associated with both obesity and insulin resistance parameters (p < 0.05). FT4 was negatively associated only with obesity parameters (p < 0.05). CONCLUSIONS: Our data strongly support that the changes of thyroid hormones may be influenced by adiposity and its metabolic consequences, such as insulin resistance. This relationship can be explained by a cross talk between adipose tissue release and thyroid function. Nevertheless, metformin treatment seems to affect thyroid function in diabetic patients by maintaining plasma thyrotropin levels to subnormal levels.

Genetic susceptibility to type 2 diabetes: a global meta-analysis studying the genetic differences in Tunisian populations.

The present study is the first meta-analysis to evaluate type 2 diabetes (T2D)- associated polymorphisms in cohorts originated from several Tunisian regions. In fact, we evaluated the effect of seven polymorphisms in the following genes-PPARg (Pro12Ala), TNFα (-308A/G), ENPP1(K121Q), TCF7L2(rs7903146°C/T), MTHFR(C677T), ACE(I/D), and CAPN10(3R/2R)-on T2D risk, through a meta-analysis combining data of previous studies performed on Tunisian populations originating from the north, center, or south of the country. R statistics version 2.12.1 software was used to estimate the heterogeneity between studies. Pooled odds ratios were computed by the fixed-effects method of Mantel-Haenszel if no heterogeneity between studies exists. Despite the similarities founded in a number of loci, the Woolf test reported that the contributions of ENPP1 and ACE loci in T2D risk are dependent on the geographic origin of concerned groups, and this heterogeneity could be attributed not only to the variable contribution of the variant in T2D risk but also to diversities of genetic background between tested groups. Interestingly, observed heterogeneity highlighted founding concerning Y chromosome and the mitochondrial DNA about the genetic structure of Tunisian population and proves once again that Tunisians, like the north-Africans, are a mosaic of subpopulations, with significant differences in genetic structure. In homogeneous groups, we replicated the association of single-nucleotide polymorphisms of TCF7L2, MTHFR, CAPN 10, TNFα, and ACE genes with a T2D risk in the Tunisian population with OR ranging from 1.43 to 6.72. However, we reported an absence of the association of PPARg with T2D in the Tunisian population.

Relationship between subcutaneous adipose tissue expression of leptin and obesity in Tunisian patients.

BACKGROUND: The incidence of obesity has dramatically increased in overall the world. It is a consequence of imbalance between energy intake and energy expenditure. Leptin is a fat derived adipokine that has emerged over the past decade as a key hormone in the regulation of food intake and energy expenditure. Elevated leptin levels are found in obese humans, suggesting a role of leptin in regulating body weight and adiposity. AIM: The aim of this study was to investigate the change of leptin mRNA expression level and its correlation with obesity and several metabolic variables in Tunisian patients. METHODS: Real time quantitative polymerase chain reaction (QPCR) analysis was carried out among two groups who underwent an abdominal surgery: controls (n = 9) and obese patients (n = 7). RESULTS: Leptin mRNA expression in subcutaneous adipose tissue was markedly increased in obese patients (p < 0.01). It was positively correlated with measures of obesity waist circumference (WC) (r = 0, 71, p < 0.01) and body mass index (BMI) (r = 0, 68, p < 0.01). Interestingly, leptin gene expression was also correlated to insulin resistance index (r = 0, 72, p < 0.01). CONCLUSION: The present study is the first investigation of leptin regulation in subcutaneous adipose tissue of Tunisian population. Our data showed that leptin levels are higher in obese subjects than in control subjects. This indicates that the subcutaneous adipose plays an important role in impaired adipokine regulation, and consequently in developing metabolic disorder.

Study of TNFalpha -308G/A and IL6 -174G/C polymorphisms in type 2 diabetes and obesity risk in the Tunisian population.

OBJECTIVES: We investigated two genetic markers in pro inflammatory molecules : TNFalpha -308G/A and IL6 -174G/C in order to assess their effect on type 2 diabetes (T2D) and obesity in the Tunisian population. DESIGN AND METHODS: The study sample includes 228 patients with T2D and 300 healthy controls. Genotyping of IL6 -174G/C (rs1800795) was performed using Automated Dye Terminator Sequencing and of TNFalpha -308G/A (rs1800629) using the LightTyper technology. RESULTS: SNPs IL6 -174G/C and TNFalpha -308G/A are associated neither with T2D (p=0.89, p=0.34 respectively) nor with risk for overweight (p=0.86, p=0.12 respectively) in Tunisian population. Bonferroni correction showed that the founded association of IL6 -174G/C SNP with T2D susceptibility restricted to overweight patients (p(nominal)=0.03, p(corrected)=0.0033) is likely to be a random result. CONCLUSION: SNPs IL6 -174G/C and TNFalpha -308G/A are not major contributors to T2D or obesity risk in our Tunisian population.