Weight loss normalizes enhanced expression of the oncogene survivin in visceral adipose tissue and blood leukocytes from individuals with obesity.

ABSTRACT

BACKGROUND/OBJECTIVES: Survivin is an oncogene associated with a decrease in apoptosis, an increase in tumor growth, and poor clinical outcome of diverse malignancies. A correlation between obesity, cancer, and survivin is reported in the literature. To date, the impact of weight loss on change in survivin levels is understudied. This study was aimed at (1) comparing survivin levels in adipose tissue (AT) from lean and obese animal models and evaluating changes after weight loss induced by energy restriction and/or exercise; (2) comparing survivin levels in normal weighted and obese humans and evaluating changes in survivin levels after weight loss induced by a very-low-calorie ketogenic diet (VLCKD) or bariatric surgery in AT and/or blood leukocytes (PBL/PBMCs). SUBJECTS/METHODS: Survivin expression was evaluated in subcutaneous (SAT) and visceral (VAT) AT derived from animal models of monogenic (Zucker rats) and diet-induced obesity (Sprague Dawley rats and C57BL/6J mice) and after a 4-week weight-loss protocol of energy restriction and/or exercise. Plasma was used to measure the inflammatory status. Survivin expression was also evaluated in PBMCs from patients with obesity and compared with normal weight, in PBLs after VLCKD, and in SAT and/or PBLs after bariatric surgery. RESULTS: Survivin expression was specifically higher in VAT from obese that lean animals, without differences in SAT. It decreased after weight loss induced by energy restriction and correlated with adiposity and inflammatory markers. In humans, the correlation between being obese and higher levels of survivin was confirmed. In obese subjects, survivin levels were reduced following weight loss after either VLCKD or bariatric surgery. Particularly, a decrease in PBMCs expression (not in SAT one) was found after surgery. CONCLUSIONS: Weight loss is effective in decreasing survivin levels. Also, PBL/PBMC should be regarded as appropriate mirror of survivin levels in VAT for the identification of an obesity-related protumoral microenvironment.