Shp2 signaling in POMC neurons is important for leptin’s actions on blood pressure, Energy balance, And glucose regulation

Jussara M. Do Carmo, Alexandre A. Da Silva, Sabira E. Ebaady, Price O. Sessums, Ralph S. Abraham, Joel K. Elmquist, Bradford B. Lowell, John E. Hall

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

Abstract

Previous studies showed that Src homology-2 tyrosine phosphatase (Shp2) is an important regulator of body weight. In this study, we examined the impact of Shp2 defi- ciency specifically in proopiomelanocortin (POMC) neurons on met- abolic and cardiovascular function and on chronic blood pressure (BP) and metabolic responses to leptin. Mice with Shp2 deleted in POMC neurons (Shp2/Pomc-cre) and control mice (Shp2flox/flox) were im- planted with telemetry probes and venous catheters for measurement of mean arterial pressure (MAP) and leptin infusion. After at least 5 days of stable control measurements, mice received leptin infusion (2µg·kg-1·day-1 iv) for 7 days. Compared with Shp2flox/flox controls, Shp2/Pomc-cre mice at 22 wk of age were slightly heavier (34±1 vs. 31±1 g) but consumed a similar amount of food (3.9±0.3 vs. 3.8±0.2 g/day). Leptin infusion reduced food intake in Shp2flox/flox mice (2.6±0.5 g) and Shp2/Pomc-cre mice (3.2±0.3 g). Despite decreasing food intake, leptin infusion increased MAP in control mice, whereas no significant change in MAP was observed in Shp2/Pomc-cre mice. Leptin infusion also decreased plasma glucose and insulin levels in controls (12±1to6±1µU/ml and 142±12 to 81±8 mg/100 ml) but not in Shp2/Pomc-cre mice. Leptin increased VO2 by 16 2% in controls and 7±1% in Shp2/Pomc-cre mice. These results indicate that Shp2 signaling in POMC neurons contributes to the long-term BP and antidiabetic actions of leptin and may play a modest role in normal regulation of body weight.

Original languageEnglish (US)
Pages (from-to)R1438-R1447
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume307
Issue number12
DOIs
StatePublished - Dec 15 2014

Keywords

  • Acute stress
  • Blood pressure
  • Energy balance
  • Glucose regulation
  • Heart rate

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

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