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Role of Shp2 in forebrain neurons in regulating metabolic and cardiovascular functions and responses to leptin

J M do Carmo1, A A da Silva1, P O Sessums1

  • 1Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS, USA.

International Journal of Obesity (2005)
|September 14, 2013
PubMed
Abstract

Insights

Forebrain Shp2 deficiency causes obesity and impairs appetite regulation. It also alters cardiovascular responses to stress and reduces leptin

Area of Science:

  • Neuroscience
  • Metabolic Regulation
  • Cardiovascular Physiology

Background:

  • Src homology 2 containing phosphatase (Shp2) is crucial for cellular signaling.
  • The role of forebrain Shp2 in metabolic and cardiovascular control is not fully understood.

Purpose of the Study:

  • To investigate the impact of forebrain Shp2 deficiency on metabolic and cardiovascular regulation.
  • To determine if forebrain Shp2 deficiency affects leptin's anorexic and cardiovascular actions.
  • To assess alterations in blood pressure and heart rate responses to stress.

Main Methods:

  • Generated forebrain-specific Shp2 knockout mice (Shp2/CamKIIα-cre).
  • Utilized telemetry for continuous monitoring of blood pressure, heart rate, and body temperature.
  • Employed indirect calorimetry to measure oxygen consumption, energy expenditure, and motor activity.

Main Results:

  • Shp2/CamKIIα-cre mice exhibited obesity, hyperglycemia, hyperleptinemia, hyperinsulinemia, and hyperphagia.
  • These mice showed reduced feeding responses to fasting/refeeding and impaired thermoregulation.
  • Despite obesity, baseline blood pressure and heart rate were similar, but responses to cold and acute stress were augmented.
  • Leptin's effects on food intake and blood pressure were significantly attenuated.

Conclusions:

  • Forebrain Shp2 signaling is essential for regulating appetite, feeding behavior, and thermoregulation.
  • Forebrain Shp2 deficiency leads to metabolic syndrome features and altered cardiovascular stress responses.
  • Impaired Shp2 signaling in the forebrain attenuates leptin's cardiovascular effects.

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