Genetic variability and telomere length in bariatric surgery outcomes in obese patients

Abstract

Based on the background showing i) that obesity have a polygenic nature with the implication of different genes of minor effect and lifestyle factors; ii) the high variability between individuals in weight loss outcome after bariatric surgery (BS) and iii) that obesity is associated with a chronic state of inflammation and oxidative stress that has been linked with accelerated ageing; the hypothesis and objectives of the present thesis are:

HYPOTHESIS: At least a set of candidate genes related with obesity will be underlying the variability in weight loss outcome after bariatric surgery in obese patients. Moreover, the weight loss, the decrease of inflammatory state and oxidative stress, experienced by obese patients after bariatric surgery will be associated with a restore of telomere length (TL) in post-operative period in those patients.

To explore this hypothesis, the following objectives were established:

MAIN OBJECTIVES: To identify specific genetic polymorphisms in candidate genes involved in the pathophysiology of obesity, clinical and sociodemographic factors that can predict long-term outcomes in patients submitted to bariatric surgery (section I). We also aim to investigate telomere length in different subtypes of obese patients, patients with depression and to examine changes in TL in relation to weight loss after bariatric surgery (section II). These objectives will be conducted in a cohort of patients with obesity submitted to bariatric surgery and followed-up for 24 months.

SPECIFIC OBJECTIVES OF SECTION I:

1. To examine the role of the FKBP5 gene, involved in the hypothalamic-pituitary- adrenal (HPA) axis, in relation to age, sex and type of surgery in weight loss after bariatric surgery in a sample of 151 severe obese patients with a 2-year follow-up after bariatric surgery.

2. To study the implication of a BDNF polymorphism (rs6265) on weight loss, and the effect of type-2 diabetes on weight changes experienced by a sample of 158 obese patients submitted to bariatric surgery with 2-year follow-up.

SPECIFIC OBJECTIVES OF SECTION II:

3. To evaluate baseline differences in telomere length in different subtypes of obese patients, and to examine longitudinal changes in telomere length after bariatric surgery over a 2-year period in a cohort of 94 obese patients.

4. To review and discuss the published evidences about telomere length in obese patients submitted to bariatric surgery to better understand how efficacious bariatric surgery as an intervention is to promote telomere length restoration.

5. To review the literature regarding telomere length and depression, a disorder highly prevalent in obese patients.