title: A role for inducible 6-phosphofructo-2-kinase in the control of neuronal glycolysis.
abstract: Increased glycolysis is the result of the sensing of glucose by hypothalamic neurons. The biochemical mechanisms underlying the control of hypothalamic glycolysis, however, remain to be elucidated. Here we showed that PFKFB3, the gene that encodes for inducible 6-phosphofructo-2-kinase (iPFK2), was expressed at high abundance in both mouse hypothalami and clonal hypothalamic neurons. In response to re-feeding, PFKFB3 mRNA levels were increased by 10-fold in mouse hypothalami. In the hypothalamus, re-feeding also decreased the phosphorylation of AMP-activated protein kinase (AMPK) (Thr172) and the mRNA levels of agouti-related protein (AgRP), and increased the mRNA levels of cocaine-amphetamine-related transcript (CART). Similar results were observed in N-43/5 clonal hypothalamic neurons upon treatment with glucose and/or insulin. In addition, knockdown of PFKFB3/iPFK2 in N-43/5 neurons caused a decrease in rates of glycolysis, which was accompanied by increased AMPK phosphorylation, increased AgRP mRNA levels and decreased CART mRNA levels. In contrast, overexpression of PFKFB3/iPFK2 in N-43/5 neurons caused an increase in glycolysis, which was accompanied by decreased AMPK phosphorylation and decreased AgRP mRNA levels and increased CART mRNA levels. Together, these results suggest that PFKFB3/iPFK2 responds to re-feeding, which in turn stimulates hypothalamic glycolysis and decreases hypothalamic AMPK phosphorylation and alters neuropeptide expression in a pattern that is associated with suppression of food intake.
authors.affiliation: Department of Nutrition and Food Science, Texas A&M University, College Station, TX 77843, USA.
authors.forename: Honggui
authors.initials: H
authors.lastname: Li
authors.forename: Xin
authors.initials: X
authors.lastname: Guo
authors.forename: Hang
authors.initials: H
authors.lastname: Xu
authors.forename: Shih-Lung
authors.initials: SL
authors.lastname: Woo
authors.forename: Vera
authors.initials: V
authors.lastname: Halim
authors.forename: Caurnel
authors.initials: C
authors.lastname: Morgan
authors.forename: Chaodong
authors.initials: C
authors.lastname: Wu
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D054369:Agouti-Related Protein / Q000235:genetics / Q000378:metabolism; D000818:Animals; D004435:Eating / Q000502:physiology; D004790:Enzyme Induction; D005947:Glucose / Q000378:metabolism*; D006019:Glycolysis; D007031:Hypothalamus / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D025481:Phosphofructokinase-2 / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein
chemical_list: D054369:Agouti-Related Protein; C515199:Agrp protein, mouse; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein; D025481:Phosphofructokinase-2; D055372:AMP-Activated Protein Kinases; D005947:Glucose