Lipolysis and apoptosis of adipocytes induced by neuropeptide Y-Y5 receptor antisense oligodeoxynucleotides in obese rats

Acta Pharmacol Sin. 2003 Jun;24(6):569-75.

Abstract

Aim: To investigate the influence of central administration of neuropeptide Y-Y5 receptor antisense oligodeoxynucleotides (ODN) on the body weight and fat pads of high-energy diet-induced obese rats, and the effects on white adipocyte lipolysis and apoptosis.

Methods: Y5 receptor antisense, sense, mismatched oligodeoxynucleotides (ODN) or vehicle were intracerebroventricularly injected, and average adipocyte area was calculated. DNA ladders were measured to evaluate adipocyte apoptosis, and RT-PCR was used to analyze the expression of bcl-2 and bax gene.

Results: (1) Central administration of Y5 receptor antisense ODN significantly decreased body weight, fat pads, and average adipocyte area. (2) DNA fragmentation was presented after electrophoresis at both epididymal and retroperitoneal adipose tissue. (3) The expression of bcl-2 gene was downregulated, while the expression of bax was upregulated.

Conclusion: Lipolysis and adipocyte apoptosis may be important reasons for Y5 receptor antisense therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipocytes / drug effects*
  • Adipocytes / pathology
  • Adipose Tissue / metabolism
  • Animals
  • Animals, Newborn
  • Apoptosis / drug effects*
  • Body Weight / drug effects
  • DNA Fragmentation
  • Lipolysis / drug effects*
  • Male
  • Obesity / metabolism
  • Obesity / pathology*
  • Oligodeoxyribonucleotides, Antisense / pharmacology*
  • Proto-Oncogene Proteins / biosynthesis
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins c-bcl-2 / biosynthesis
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • RNA, Messenger / genetics
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Neuropeptide Y / antagonists & inhibitors*
  • Receptors, Neuropeptide Y / genetics
  • bcl-2-Associated X Protein

Substances

  • Bax protein, rat
  • Oligodeoxyribonucleotides, Antisense
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • RNA, Messenger
  • Receptors, Neuropeptide Y
  • bcl-2-Associated X Protein
  • neuropeptide Y5 receptor