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Protein tyrosine phosphatase-1B contributes to LPS-induced leptin resistance in male rats

Beatriz de Carvalho Borges1, Rodrigo C Rorato1, Ernane Torres Uchoa1

  • 1Department of Physiology, School of Medicine of Ribeirão Preto, University of São Paulo, Brazil; and.

American Journal of Physiology. Endocrinology and Metabolism
|October 30, 2014
PubMed

Insights

Repeated lipopolysaccharide (LPS) exposure increases tyrosine phosphatase-1B (PTP1B) in the hypothalamus, causing leptin resistance. Inhibiting PTP1B restores leptin sensitivity, suggesting PTP1B

Area of Science:

  • Neuroendocrinology
  • Molecular Biology
  • Physiology

Background:

  • Leptin resistance, a hallmark of obesity, is linked to altered signaling pathways involving tyrosine phosphatases.
  • Lipopolysaccharide (LPS) exposure can induce inflammatory states that may contribute to leptin resistance.
  • Tyrosine phosphatase-1B (PTP1B) and SHP-2 are key regulators of leptin receptor signaling.

Purpose of the Study:

  • To investigate the role of PTP1B and SHP-2 in lipopolysaccharide (LPS)-induced leptin resistance in the rat hypothalamus.
  • To determine the effects of single versus repeated LPS administration on hypothalamic signaling and leptin responsiveness.

Main Methods:

  • Male Wistar rats received single or repeated intraperitoneal LPS injections.
  • Expression of PTP1B, SHP-2, p-ERK1/2, and p-STAT3 was analyzed in hypothalamic tissue.
  • Leptin's effects on food intake, body weight, and STAT3 phosphorylation were assessed.
  • A PTP1B inhibitor was administered intracerebroventricularly to evaluate its impact on leptin resistance.

Main Results:

  • Repeated LPS treatment increased hypothalamic PTP1B expression and decreased SHP-2, while p-STAT3 levels remained unchanged.
  • Repeated LPS exposure induced leptin resistance, evidenced by the lack of leptin's effect on food intake, body weight, and p-STAT3.
  • PTP1B inhibition restored leptin sensitivity, including reduced food intake, body weight loss, and STAT3 phosphorylation in LPS-treated rats.

Conclusions:

  • Increased hypothalamic PTP1B expression is a key mechanism underlying leptin resistance induced by repeated LPS exposure.
  • Targeting PTP1B may offer a therapeutic strategy for leptin resistance associated with low-grade inflammation and obesity.
Keywords:
Src homology 2 domain-containing tyrosine phosphatase-2endotoxemiaextracellular signal-regulated kinasesleptin resistanceprotein tyrosine phosphatase-1B

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