title: 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.affiliation: Department of Physiology and Biophysics, Mississippi Center for Obesity Research, and Cardiovascular-Renal Research Center, University of Mississippi Medical Center, Jackson, Mississippi; jdocarmo@umc.edu.
authors.forename: Jussara M
authors.initials: JM
authors.lastname: do Carmo
authors.affiliation: Department of Physiology and Biophysics, Mississippi Center for Obesity Research, and Cardiovascular-Renal Research Center, University of Mississippi Medical Center, Jackson, Mississippi;
authors.forename: Alexandre A
authors.initials: AA
authors.lastname: da Silva
authors.affiliation: Department of Physiology and Biophysics, Mississippi Center for Obesity Research, and Cardiovascular-Renal Research Center, University of Mississippi Medical Center, Jackson, Mississippi;
authors.forename: Sabira E
authors.initials: SE
authors.lastname: Ebaady
authors.affiliation: Department of Physiology and Biophysics, Mississippi Center for Obesity Research, and Cardiovascular-Renal Research Center, University of Mississippi Medical Center, Jackson, Mississippi;
authors.forename: Price O
authors.initials: PO
authors.lastname: Sessums
authors.affiliation: Department of Physiology and Biophysics, Mississippi Center for Obesity Research, and Cardiovascular-Renal Research Center, University of Mississippi Medical Center, Jackson, Mississippi;
authors.forename: Ralph S
authors.initials: RS
authors.lastname: Abraham
authors.affiliation: Department of Pharmacology and Division of Hypothalamic Research, Department of Internal Medicine, Utah Southwestern Medical Center, Dallas, Texas; and.
authors.forename: Joel K
authors.initials: JK
authors.lastname: Elmquist
authors.affiliation: Division of Endocrinology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts.
authors.forename: Bradford B
authors.initials: BB
authors.lastname: Lowell
authors.affiliation: Department of Physiology and Biophysics, Mississippi Center for Obesity Research, and Cardiovascular-Renal Research Center, University of Mississippi Medical Center, Jackson, Mississippi;
authors.forename: John E
authors.initials: JE
authors.lastname: Hall
mesh_terms: D000818:Animals; D062186:Arterial Pressure / Q000187:drug effects*; D001786:Blood Glucose / Q000187:drug effects* / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000201:enzymology; D004435:Eating / Q000187:drug effects; D004734:Energy Metabolism / Q000187:drug effects*; D006706:Homeostasis; D007262:Infusions, Intravenous; D007328:Insulin / Q000097:blood; D020738:Leptin / Q000008:administration & dosage*; D008297:Male; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity / Q000187:drug effects; D009474:Neurons / Q000187:drug effects* / Q000201:enzymology; D010101:Oxygen Consumption / Q000187:drug effects; D011333:Pro-Opiomelanocortin / Q000378:metabolism*; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D013997:Time Factors
chemical_list: D001786:Blood Glucose; D007328:Insulin; D020738:Leptin; D011333:Pro-Opiomelanocortin; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; C516725:Ptpn11 protein, mouse
keywords: acute stress; blood pressure; energy balance; glucose regulation; heart rate