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SH 2‐Containing Inositol 5′‐Phosphatase 2 Selectively Impairs Hypothalamic Insulin Signalling and Regulation of Food Intake in Mice
Author(s) -
Ichihara Y.,
Wada T.,
Soeda Y.,
Ishii Y.,
Sasahara M.,
Tsuneki H.,
Sasaoka T.
Publication year - 2013
Publication title -
journal of neuroendocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.062
H-Index - 116
eISSN - 1365-2826
pISSN - 0953-8194
DOI - 10.1111/jne.12014
Subject(s) - medicine , endocrinology , hypothalamus , leptin , insulin , biology , insulin receptor , neuropeptide y receptor , phosphatidylinositol , phosphorylation , chemistry , neuropeptide , receptor , insulin resistance , microbiology and biotechnology , obesity
SH 2‐containing inositol 5′‐phosphatase 2 ( SHIP 2) is a lipid phosphatase that negatively regulates the metabolic signalling of insulin in peripheral tissues; however, the expression of SHIP 2 in the hypothalamus and its functional roles are largely unknown. In the present study, immunohistochemical analysis demonstrated that SHIP 2 protein exists in neuronal cells expressing neuropeptide Y and pro‐opiomelanocortin in the arcuate nucleus of the hypothalamus in C57 BL /6J mice. Interestingly, the expression levels of SHIP 2 in the hypothalamus were elevated in aged C57 BL /6J mice and diabetic db/db mice. To clarify the significance of the increased expression of SHIP 2 in the hypothalamus, we examined the central effects of insulin and leptin in transgenic mice overexpressing SHIP 2 ( SHIP 2‐Tg). Accumulation of phosphatidylinositol (3,4,5)‐trisphosphate and phosphorylation of Akt in the hypothalamus, induced by i.c.v. injection of insulin, were attenuated in SHIP 2‐Tg compared to wild‐type mice, whereas leptin‐induced phosphorylation of signal transducer and activator of transcription 3 in the hypothalamus was comparable between them. The suppression of food intake after i.c.v. administration of insulin (but not leptin) was attenuated consistently in SHIP 2‐Tg. In addition, SHIP 2‐Tg showed increased food consumption after starvation and become heavier with visceral fat accumulation than wild‐type mice, despite normal levels of oxygen consumption and spontaneous movement. These results suggest that SHIP 2 contributes to the regulation of food intake mainly via the attenuation of insulin signalling in the hypothalamus of mice.