Associations between obesity-related gene expression in maternal and cord blood and newborn adiposity: findings from the Araraquara Cohort study.

BACKGROUND/OBJECTIVES: Genes involved in the regulation of metabolism, adipose tissue deposition, inflammation, and the appetite-satiety axis may play an important role in fetal development, and possibly induce permanent metabolic changes and fat accumulation. In this study we investigated: (1) obesity-related gene expression in maternal and cord blood of overweight/obese and normal-weight pregnant women; (2) associations between obesity-related gene expression in maternal and cord blood; and (3) associations of gene expression in each of maternal and cord blood with newborn adiposity. SUBJECTS/METHODS: Twenty-five overweight/obese and 32 normal-weight pregnant women were selected from the Araraquara Cohort Study according to their pre-pregnancy BMI. Maternal and cord blood gene expression of LEPR, STAT3, PPARG, TLR4, IL-6, IL-10, FTO, MC4R, TNF-α, and NFκB were investigated by relative real-time PCR quantification. The body composition of the newborns was assessed by air displacement plethysmography. Associations between maternal and cord blood gene expression and markers of newborn adiposity (weight, BMI, and fat mass%) were explored by linear regression models controlling for maternal age, pre-pregnancy BMI, maternal gestational weight gain, gestational age, and newborn sex. RESULTS: There was higher TLR4, NFκB, and TNF-a expression, and lower IL-6 expression, in overweight/obese pregnant women and their respective newborns compared with normal-weight women and their newborns (p < 0.001). Maternal PPARG gene expression was associated with both weight and fat mass % of the newborns, and cord blood IL-10 expression was associated with BMI and fat mass %, controlling for confounders. CONCLUSION: To our knowledge, this is the first study to evaluate the relationship of maternal and cord blood gene expression with adiposity markers of the newborn. Our results provide evidence for the contribution of maternal and cord blood gene expression-particularly maternal PPARG and TLR4 expression, and cord blood IL-10 expression-to newborn weight, BMI, and fat mass %.

Cytotoxicity analysis of EDTA and citric acid applied on murine resident macrophages culture.

AIM: To assess the ex vivo cytotoxicity of EDTA and citric acid solutions on macrophages. METHODOLOGY: The cytotoxicity of 17% EDTA and 15% citric acid was evaluated on murine macrophage cultures using MTT-Tetrazolium method [3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyl tetrazolium bromide]. A total of 5 x 10(5) cells were plated in medium culture with 17% EDTA or 15% citric acid. Fresh medium was used as a control. Toxicity values were analysed statistically by anova and Tukey's test (P<0.05) at short (0, 6, 12, 24 h) and medium periods (1, 3, 5, 7 days), using ELISA absorbance. RESULTS: On the short term, both EDTA (0.253 nm) and citric acid (0.260 nm) exhibited cytotoxic effects on macrophage cultures (P<0.05). On the medium term, statistical differences were observed (P<0.05) between the groups. EDTA (0.158 nm) and citric acid (0.219 nm) were cytotoxic when compared with the control group; EDTA-reduced macrophage viability significantly more than citric acid (P<0.05). CONCLUSIONS: Both EDTA and citric acid had effects on macrophages cells ex vivo, but citric acid was less toxic in periods from 1 to 7 days of use.

Protein-energy malnutrition alters histological and ultrastructural characteristics of the bone marrow and decreases haematopoiesis in adult mice.

Protein-energy malnutrition (PEM) decreases resistance to infection by impairing a number of physiological processes, including haematopoiesis. The aim of this study was to evaluate the microanatomical aspects of bone marrow (BM) in mice that were subjected to PEM, in particular, with respect to the components of the local extracellular matrix and the proliferative activity of haematopoietic cells. For this, histological, histochemical, immunohistochemical and ultrastructural techniques were used. Two-month old male Swiss mice were fed with a low-protein diet containing 4% protein and control mice fed a 20% protein diet. When the experimental group had attained a 25% loss of their original body weight, we collected the different biological samples. Malnourished mice had presented severe BM atrophy as well as a reduction in proliferating cell nuclear antigen and gelatinous degeneration. The malnourished mice had more fibronectin accretion in paratrabecular and endosteal regions and more laminin deposition in perisinusal sites than controls. Endosteal cell activation and hyperplasia were found, suggesting their participation in the process. Additionally, we have observed a decrease in the capacity of malnourished haematopoietic stroma to support the growth of haematopoietic stem cells (CD34+) in vitro. These findings point to a structural impairment of the haematopoietic microenvironments in mice with PEM, possibly hampering the interactions between cells and cellular signalling.