Changes in adipose tissue lipolysis gene expression and insulin sensitivity after weight loss

Abstract

Objective: Insulin resistance is a major pathophysiological link between obesity and its metabolic complications. Weight loss (WL) is an effective tool t o prevent obesity-related diseases; however, the mechanisms of an improvement in insulin sensitivity (IS) after weight-reducing interventions are not completely understood. The aim of the present study was to analyze the relationships between IS and adipose t issue (AT) expression of the genes involved in the regulation of lipolysis in obese subj ects after WL. Methods: Fifty-two obese subjects underwent weight-reducing dietary int ervention program. The control group comprised 20 normal-weight subjects, examined at baseline only. Hyperinsulinemic-euglycemic clamp and s.c. AT biopsy with subsequent gene expression analysis were performed before and after the program . Results: AT expression of genes encoding lipases (PNPLA2, LIPE and MGLL) and lipid-droplet proteins enhancing (ABHD5) and inhibiting lipolysis (PLIN1 and CIDEA) were decreased in obese individuals in comparison with normal-weight individuals. The group of 38 obese participants completed dietary intervention program and clamp studies, which resulted in a significant WL and an improvement in mean IS . However, in nine subjects from this group IS did not improve in response to WL. AT expression of PNPLA2, LIPE and PLIN1 increased only in the group without IS improvement. Conclusions: Excessive lipolysis may prevent an improvement in IS during WL . The change in AT PNPLA2 and LIPE expression was a negative predictor of the change in IS after WL.

Keywords

• weight loss
• insulin sensitivity
• adipose tissue
• hormone-sensitive lipase
• adipose triglyceride lipase