Necdin-E2F4 interaction provides insulin-sensitizing effect after weight loss induced by gastric bypass surgery

Zehra N. Pamuklar, Jiegen Chen, Michael Muehlbauer, Anna Spagnoli, Alfonso Torquati

Research output: Contribution to journalArticle

1 Scopus citations

Abstract

Background: The insulin-like growth factor-1 (IGF-1) signaling pathway promotes adipocyte differentiation and, therefore, insulin sensitivity by suppression of necdin expression, which represses peroxisome proliferator-activated receptor-gamma promoter activity by interaction with E2F4 in mouse adipocytes. The aim of the present study was to test the hypothesis that this pathway represents one of the mechanisms by which Roux-en-Y gastric bypass surgery (RYGB) induces resolution of insulin resistance. Methods: Clinical samples were collected and the key biomarkers measured to test the hypothesis that the IGF-1 pathway represents 1 of the mechanisms by which RYGB induces resolution of insulin resistance in obese individuals. Results: Free IGF-1 levels were significantly greater in the post-RYGB patients than in the pre-RYGB obese patients (2.55 ± 1.54 versus 1.32 ±.65 μg/L, P =.03) and similar to that in normal weight controls (2.54 ± 1.27 μg/L). Necdin and E2F4 gene expression in the adipose tissue was significantly downregulated after RYGB compared with obese and were similar to the levels observed in the controls. In mature human adipocytes cultured in vitro, treatment with des-IGF-1 induced downregulation of necdin and E2F4 gene expression in a dose-dependent manner (P =.01). Conclusion: After RYGB, the insulin/IGF-1 signaling pathway is activated and could account for the observed decrease in the expression of necdin, which represses peroxisome proliferator-activated receptor-gamma promoter activity by interaction with E2F4. This could represent one of the mechanisms that induce resolution of insulin resistance after RYGB.

Original languageEnglish (US)
Pages (from-to)94-99
Number of pages6
JournalSurgery for Obesity and Related Diseases
Volume9
Issue number1
DOIs
Publication statusPublished - Jan 1 2013

    Fingerprint

Keywords

  • Adipocyte
  • Adipose tissue
  • Bariatric surgery
  • E2F4
  • Gastric bypass surgery
  • Necdin

ASJC Scopus subject areas

  • Surgery

Cite this