Shp2 signaling in POMC neurons is important for leptin's actions on blood pressure, energy balance, and glucose regulation.

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 deficiency specifically in proopiomelanocortin (POMC) neurons on metabolic 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 (Shp2(flox/flox)) were implanted 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 (2 μg·kg(-1)·day(-1) iv) for 7 days. Compared with Shp2(flox/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 Shp2(flox/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 ± 1 to 6 ± 1 μU/ml and 142 ± 12 to 81 ± 8 mg/100 ml) but not in Shp2/Pomc-cre mice. Leptin increased V̇o2 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.

• Authors: 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
• Journal: American journal of physiology. Regulatory, integrative and comparative physiology (Am J Physiol Regul Integr Comp Physiol) Vol. 307 Issue 12 Pg. R1438-47 (Dec 15 2014) ISSN: 1522-1490 [Electronic] United States
• PMID: 25339680 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 the American Physiological Society.

Chemical References

• Blood Glucose
• Insulin
• Leptin
• Pro-Opiomelanocortin
• Protein Tyrosine Phosphatase, Non-Receptor Type 11
• Ptpn11 protein, mouse

Topics

• Animals
• Arterial Pressure (drug effects)
• Blood Glucose (drug effects, metabolism)
• Body Weight (drug effects)
• Brain (drug effects, enzymology)
• Eating (drug effects)
• Energy Metabolism (drug effects)
• Homeostasis
• Infusions, Intravenous
• Insulin (blood)
• Leptin (administration & dosage)
• Male
• Mice, 129 Strain
• Mice, Inbred C57BL
• Mice, Knockout
• Motor Activity (drug effects)
• Neurons (drug effects, enzymology)
• Oxygen Consumption (drug effects)
• Pro-Opiomelanocortin (metabolism)
• Protein Tyrosine Phosphatase, Non-Receptor Type 11 (deficiency, genetics, metabolism)
• Signal Transduction (drug effects)
• Time Factors