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A role of PFKFB3/iPFK2 in the regulation of neuronal glycolysis and food intake
Author(s) -
Guo Xin,
Li Honggui,
Wu Chaodong
Publication year - 2009
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.23.1_supplement.973.1
Subject(s) - glycolysis , ampk , gene knockdown , phosphorylation , protein kinase a , endocrinology , medicine , biology , hypothalamus , neuropeptide y receptor , microbiology and biotechnology , amp activated protein kinase , chemistry , neuropeptide , metabolism , biochemistry , gene , receptor
Glycolysis is crucial for hypothalamic neurons to sense glucose. However, the biochemical mechanism underlying the control of hypothalamic glycolysis is not well understood. Here we show that PFKFB3, a gene whose product controls glycolysis, is predominantly expressed in both mouse hypothalami and clonal hypothalamic neurons. In response to feeding, PFKFB3 expression is dramatically increased in mouse hypothalami. In addition, the increased PFKFB3 expression is accompanied by decreased phosphorylation of hypothalamic AMP‐activated protein kinase (AMPK), as well as decreased Agouti‐related protein (AgRP) expression and increased cocaine‐amphetamine‐related transcript (CART) expression. Similar results are observed in cultured hypothalamic neurons in response to glucose and insulin. Upon knockdown or overexpression of PFKFB3 in cultured hypothalamic neurons, glycolysis rates are altered, which in turn lead to changes in AMPK phosphorylation and neuropeptide expression. Furthermore, in hyperphagic mice, central overexpression of PFKFB3 causes a significant decrease in food intake, which contributes to a reduction in body weight. Taken together, our data suggest that PFKFB3 responds to feeding‐regulatory signals to govern hypothalamic glycolysis and in turn modulates AMPK phosphorylation and neuropeptide expression to regulate food intake.