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Metabolic and appetite responses to fasting and refeeding in mice with Shp2 deletion in forebrain neurons
Author(s) -
Carmo Jussara M,
Silva Alexandre A,
Hall John E
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.877.2
Subject(s) - medicine , endocrinology , appetite , forebrain , energy homeostasis , regulator , homeostasis , body weight , biology , obesity , chemistry , central nervous system , biochemistry , gene
Previous studies showed that Src homology‐2 tyrosine phosphatase (Shp2) is an important regulator of body weight homeostasis. Whether Shp2 is involved in normal refeeding response after prolonged fasting is still unknown. In this study we examined whether mice with Shp2 deletion in forebrain neurons (Shp2/CamK2‐Cre mice) exhibit impaired appetite and metabolic responses to refeeding after 24‐hrs of fasting. Shp2/CamK2‐Cre (n=6) and control mice (Shp2flox/flox, n=5) at 22‐weeks of age were placed in a controlled apparatus to measure 24‐hr food intake (FI), oxygen consumption (VO2), and body core temperature (BT) before and after a 24‐hr fasting protocol. Shp2/CamK2‐Cre mice were heavier, hyperphagic (4.7±0.3 vs. 3.0±0.3 g), exhibited lower VO2, but similar BT. Fasting reduced body weight (52.0±3.8 to 48.6±3.6 and 32.9±2.2 to 30.3±2.4 g), VO2 (2154±135 to 1898±138 and 2424±197 to 2093±132 ml/kg/hr), and BT (36.5±0.2 to 35.4 ±0.2 and 36.2±0.0 to 35.5±0.1 oC) in Shp2/CamK2‐Cre and Shp2flox/flox mice. The increases in metabolic rate and appetite in response to refeeding were attenuated in Shp2/CamK2‐ Cre compared to control mice (VO2: +6 vs. +11% and FI: +6 vs. +54%). Our results demonstrate that in addition to promote obesity, Shp2 deletion in forebrain neurons is also involved in the normal FI and metabolic responses to refeeding after prolonged fasting. (NHLBI‐PO1HL51971/AHA SDG5680016)