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Expression of constitutively active Jak2 in the hypothalamus leads to weight gain that correlates with increased SOCS3 levels
Author(s) -
Ryder Daniel J,
Nabilsi Nancy,
Sayeski Peter,
Scarpace Philip
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.lb147
Subject(s) - socs3 , leptin , hypothalamus , medicine , endocrinology , biology , transgene , leptin receptor , weight gain , signal transduction , obesity , body weight , microbiology and biotechnology , gene , biochemistry , stat3
The leptin pathway is of great clinical interest for weight loss. However, intricate feedback signals obscure viable strategies to affect leptin‐mediated weight loss. We aim to understand this pathway and determine if a constitutively active positive regulator of leptin signaling, Jak2 V617F, alters weight gain and energy intake. Hypothalamic injection of pLentiV617F and pLenti‐GFP was carried out. Rats were given high fat diet and monitored for food intake/weight changes. Oxygen consumption and fat pad analysis was conducted. After tissue extraction QPCR was used to verify expression of transgenes and evaluate levels of endogenous Jak2 transcript and immunoblot to measure Jak2 and SOCS3 protein. Body weight, intake and food efficiency for the V617F rats was up. Concordantly, respiration and voluntary wheel running activity was down. Transgene expression was elevated, as expected, along with leptin and hypothalamic SOCS3 protein in V617F‐injected rats. V617F is indicated to cause caloric increase and metabolic decrease. SOCS3 was up, indicating induction of an inhibitory pathway. We suspect this obese phenotype is caused by an inhibition of Jak2 signaling by SOCS3 in the hypothalamus. This delicate balance between Jak2 expression and metabolic/energy intake regulation and stands as a cautionary tale for pharmacologists who choose to alter these proteins by pharmacological means.