Background and aims: Obesity is a chronic multifactorial disease characterized by an excessive accumulation of body fat resulting from an imbalance between energy intake and caloric expenditure. Uncoupling protein 2 (UCP2) is located in the inner mitochondrial membrane and plays an important role in the regulation of energy expenditure. NLR family, pyrin domain-containing 3 (NLRP3) inflammasome seems to have a key role in obesity-induced inflammation through production of the pro-inflammatory cytokines IL-1β and IL-18. Accordingly, a number of studies have suggested that UCP2 and NLRP3 have important roles in obesity. In addition, the microRNA (miR)-133a-3p regulates UCP2 expression and appears to be involved in the activation of NLRP3 inflammasome through UCP2 blockade. However, to date, no study has evaluated the combined association of UCP2, NLRP3 and miR-133a-3p expressions with obesity. Thus, we compared UCP2, NLRP3 and miR-133a-3p expressions in subcutaneous adipose tissue (SAT) of patients with obesity and eutrophic individuals. We also evaluated if these genes correlate with body composition parameters, insulin resistance, and glycemic and lipid profiles.
Methods: SAT biopsies were obtained from 61 individuals who underwent bariatric surgery or elective abdominal surgery. Patients were divided into three groups according to body mass index (BMI): Group 1 (BMI ≤ 25 kg/m2, n=8); Group 2 (BMI: 30.0 39.9 kg/m2, n=24); and Group 3 (BMI ≥ 40 kg/m2; n=29). All subjects underwent physical and laboratory evaluations. UCP2, NLRP3 and miR-133a expressions were quantified using real-time qPCR.
Results: UCP2 expression was decreased in SAT from patients with obesity (Groups 2+3) compared to Group 1 [Group 3: median 1.1 (0.9 1.6, 25th 75th percentiles) and Group 2: 1.2 (0.9 1.5) vs. Group 1: 2.2 (1.6 2.5) n-fold changes; P=0.031]. MiR-133a-3p expression was also downregulated in patients with obesity [Group 3: 1.6 (0.9 2.5) and Group 2: 0.9 (0.5 8.5) vs. Group 1: 13.5 (3.5 33.2); P=0.029]. NLRP3 expression did not differ between groups (P=0.238); however, it was positively correlated with waist circumference and weight excess. NLRP3 expression was also positively correlated with miR-133a-3p expression and negatively correlated with UCP2 expression.
Conclusion: UCP2 and miR-133a-3p expressions are downregulated in patients with obesity. Although NRLP3 expression did not differ between groups, it was positively correlated with waist circumference and weigh excess values.
18 - 21 May 2019
European Society of Endocrinology