Abdominal Obesity and Stress in Rural and Urban Populations: an Epigenetic Approach

Name: FLÁVIA VITORINO FREITAS

Publication date: 11/06/2018
Advisor:

Namesort descending Role
ADRIANA MADEIRA ALVARES DA SILVA Advisor *

Examining board:

Namesort descending Role
ADRIANA MADEIRA ALVARES DA SILVA Advisor *
FLAVIA DE PAULA (M/D) Internal Examiner *
JOSÉ LUIZ MARQUES ROCHA External Examiner *
MARCELO DOS SANTOS External Examiner *

Summary: Hyperactivation of the hypothalamic-pituitary-adrenal axis is related to psychosocial stress and excessive accumulation of adipose tissue. The objective of this study was to identify indicators of psychosocial stress associated with abdominal adiposity and to evaluate the weight excess and methylation relationship of the glucocorticoid receptor gene promoter region (NR3C1 1F region) in adults. This cross-sectional study was performed with 384 adult subjects (20 to 59 years), users of the Unified Health System of a city in the Southeast of Brazil. The Body Mass Index (BMI) was used as an indicator of weight excess and abdominal adiposity (dependent variable) was assessed by the waist circumference. The independent variables were the indicators of psychosocial stress: Food and Nutritional Insecurity, serum cortisol, symptoms suggestive of depression by Beck Depression Inventory and altered blood pressure. Univariate linear regression models between abdominal adiposity and each indicator of stress were tested, stratified by rural and urban location, and later were adjusted for socioeconomic, health and lifestyle variables. Biochemical and molecular analyzes were performed with a sub-sample of 282 individuals grouped for BMI (&#8805; and < 25 kg/m2). The methylation profile of NR3C1 1F region was evaluated by the pyrosequencing method. By factorial analysis the inter-relationship between the specific CpG site methylation was evaluated and the main components were extracted, obtaining two Bins of CpGs. Comparisons of medians, Spearman correlations and Poisson regression with robust variance were used to evaluate the association between weight excess and methylation of NR3C1 1F region. The prevalence of weight excess was 68.3% and 71.5% of the subjects presented an increased risk for metabolic complications related to abdominal adiposity. The indicators of stress associated with abdominal adiposity were: cortisol in the rural population and altered blood pressure in the urban population. The sub-sample did not differ from the total sample for weight excess and covariates. The weight excess group had lower methylation percentages than the whithout weight excess group in the analyzes of the total segment (p <0.05), the CpGs Bins (p <0.05) and the specific CpGs site: 41, 42, 44 and 45 (p-corrected &#8804; 0.037). Hypomethylation in the total segment and in Bin 1 was explained by the weight excess, when controlled by covariates. Finally, the results point to the influence of the local and psychosocial environment on the stress modulation once the prediction of rural and urban abdominal adiposity was explained by different indicators of stress. In addition, weight excess was related to hypomethylation of NR3C1 1F region, narrowing the relationship between psychosocial stress and excessive fat accumulation.

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