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.

Fig. 1. Survivin expression (gene and protein) in AT from obese Zucker rats after weight-loss intervention.

Survivin gene expression (a) and protein levels (b) in SAT and VAT from lean and obese animals. Effect of 4 weeks of weight-loss interventions on survivin expression compared with that in the obese ad libitum group. Survivin gene expression (c) and protein levels (d) in SAT. Survivin gene expression (e) and protein levels (f) in VAT. Correlation between survivin transcript levels in VAT and FM (g), and MCP-1 (h). Data are represented as the mean ± SEM, n = 10 animals/group. ^aP < 0.05 vs. Ob AL, ^bP < 0.05 vs. Ob ER, and ^cP < 0.05 Ob EX. Ob AL were evaluated by univariant ANOVA and Bonferroni post hoc tests. Ob Al obese ad libitum group, Ob ER obese energy restriction group, Ob EX obese exercise group, Ob EREX obese energy restriction plus exercise group.

Fig. 2. Survivin gene expression in humans related with adiposity grade.

a Survivin gene expression in PBMCs in normal-weight subjects compared with patients with obesity. Data are represented as the mean ± SEM, n = 22–29 subjects/group. ^aP < 0.05 vs. normal weight, evaluated by Student's t test. b Correlation between the survivin transcripts levels in PBMCs and BMI in a group of healthy with obesity and normal-weight patients. c Survivin gene expression in PBL in patients with obesity after VLCKD treatment. Data are represented as the mean ± SEM, n = 25 subjects/group. ^aP < 0.05 vs. baseline. d Correlation between the survivin transcript levels in PBLs and BMI in humans following a VLCKD. e Survivin gene expression in SAT and PBMCs from patients with obesity following bariatric surgery. Data are represented as the fold change in survivin transcript levels after bariatric surgery and were obtained from previously published studies following bariatric surgery-induced weight loss at 2 years (¹Ortega study [32]), at 1 year (²Dankel study [33]), and at 6 months (³Pinhel study [34]). ^aP < 0.05 vs. before bariatric surgery intervention.