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2014 ; 307
(12
): R1438-47
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Shp2 signaling in POMC neurons is important for leptin s actions on blood
pressure, energy balance, and glucose regulation
#MMPMID25339680
do Carmo JM
; da Silva AA
; Ebaady SE
; Sessums PO
; Abraham RS
; Elmquist JK
; Lowell BB
; Hall JE
Am J Physiol Regul Integr Comp Physiol
2014[Dec]; 307
(12
): R1438-47
PMID25339680
show ga
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 ?g·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 ?U/ml and 142 ± 12 to 81 ± 8 mg/100 ml) but
not in Shp2/Pomc-cre mice. Leptin increased V?o2 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.
|Animals
[MESH]
|Arterial Pressure/*drug effects
[MESH]
|Blood Glucose/*drug effects/metabolism
[MESH]
|Body Weight/drug effects
[MESH]
|Brain/*drug effects/enzymology
[MESH]
|Eating/drug effects
[MESH]
|Energy Metabolism/*drug effects
[MESH]
|Homeostasis
[MESH]
|Infusions, Intravenous
[MESH]
|Insulin/blood
[MESH]
|Leptin/*administration & dosage
[MESH]
|Male
[MESH]
|Mice, 129 Strain
[MESH]
|Mice, Inbred C57BL
[MESH]
|Mice, Knockout
[MESH]
|Motor Activity/drug effects
[MESH]
|Neurons/*drug effects/enzymology
[MESH]
|Oxygen Consumption/drug effects
[MESH]
|Pro-Opiomelanocortin/*metabolism
[MESH]
|Protein Tyrosine Phosphatase, Non-Receptor Type
11/deficiency/genetics/*metabolism
[MESH]