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Protein tyrosine phosphatase 1B reduction regulates adiposity and expression of genes involved in lipogenesis

Cristina M Rondinone1, James M Trevillyan, Jill Clampit

  • 1Metabolic Diseases Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, Illinois 60064, USA. cristina.rondinone@abbott.com

Diabetes
|July 30, 2002
PubMed

Insights

Targeting protein tyrosine phosphatase 1B (PTP1B) with antisense therapy reduced fat storage and lipogenesis in obese mice. This suggests PTP1B plays a key role in obesity development and adipocyte enlargement.

Area of Science:

  • Biochemistry
  • Metabolic disease research
  • Obesity research

Background:

  • Protein tyrosine phosphatase 1B (PTP1B) is a negative regulator of insulin signaling.
  • PTP1B overexpression is linked to insulin resistance and obesity.
  • PTP1B knockout mice show enhanced insulin sensitivity and resistance to weight gain.

Purpose of the Study:

  • To investigate the role of PTP1B in adipose tissue of obese animals.
  • To assess the effects of PTP1B antisense oligonucleotide (ISIS-113715) treatment on obesity and lipogenesis in hyperglycemic obese (ob/ob) mice.

Main Methods:

  • Hyperglycemic obese (ob/ob) mice were treated with PTP1B antisense oligonucleotide (ISIS-113715).
  • Adiposity, PTP1B protein levels, triglyceride content, and gene expression in adipose tissue were analyzed.
  • Key lipogenic and adipogenic genes, insulin signaling proteins, and protein kinase B phosphorylation were assessed.

Main Results:

  • Antisense treatment significantly reduced adiposity and PTP1B protein levels in fat tissue.
  • Triglyceride content in adipocytes was influenced, with downregulation of lipogenic genes (SREBP1, spot14, FAS).
  • Increased IRS-2 protein and differential regulation of p85alpha isoforms were observed, but insulin sensitivity via Akt phosphorylation was not enhanced.

Conclusions:

  • PTP1B antisense treatment effectively modulates fat storage and lipogenesis in adipose tissue.
  • PTP1B is implicated in adipocyte enlargement and the development of obesity.
  • Targeting PTP1B may offer therapeutic potential for managing obesity and related metabolic disorders.

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