title: Leptin controls ketone body utilization in hypothalamic neuron.
abstract: Leptin is an appetite-controlling peptide secreted from adipose tissue. Previously, we showed that the gene expression of acetoacetyl-CoA synthetase (AACS), the ketone body-utilizing enzyme for lipid synthesis, was suppressed by leptin deficiency-induced obesity in white adipose tissue. In this study, to clarify the effects of leptin on ketone body utilization in the central nervous system, we examined the effects of leptin signaling on AACS expression. In situ hybridization analysis of ob/ob and db/db mice revealed that AACS mRNA level was reduced by leptin deficiency in the arcuate nucleus (Arc) and ventromedial hypothalamic nucleus (VMH) in hypothalamus but not in other brain regions. Moreover, AACS mRNA level was increased by leptin treatment both in primary cultured neural cells and in N41 neural-like cells. In N41 cells, AACS level was decreased by AMPK inducer but increased by AMPK inhibitor. These results suggest that the up-regulation of AACS expression by leptin is due to the suppression of AMPK activity via neural leptin signaling and that the deficiency of this regulation may be responsible for neurological disorders in central appetite control.
authors.affiliation: Department of Health Chemistry, Hoshi University, 2-4-41, Ebara, Shinagawa-ku, Tokyo 142-8501, Japan.
authors.forename: Ryota
authors.initials: R
authors.lastname: Narishima
authors.forename: Masahiro
authors.initials: M
authors.lastname: Yamasaki
authors.forename: Shinya
authors.initials: S
authors.lastname: Hasegawa
authors.forename: Saki
authors.initials: S
authors.lastname: Yoshida
authors.forename: Shinya
authors.initials: S
authors.lastname: Tanaka
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Fukui
mesh_terms: D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D003066:Coenzyme A Ligases / Q000235:genetics / Q000378:metabolism; D015256:Coenzyme A-Transferases / Q000235:genetics / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007031:Hypothalamus / Q000166:cytology*; D007657:Ketone Bodies / Q000378:metabolism*; D020738:Leptin / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008820:Mice, Obese; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D011720:Pyrazoles / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D054411:Receptors, Leptin / Q000235:genetics / Q000378:metabolism; D012265:Ribonucleotides / Q000494:pharmacology; D013997:Time Factors; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: D004791:Enzyme Inhibitors; D007004:Hypoglycemic Agents; D007657:Ketone Bodies; D020738:Leptin; D011720:Pyrazoles; D011743:Pyrimidines; D012333:RNA, Messenger; D054411:Receptors, Leptin; D012265:Ribonucleotides; C515447:leptin receptor, mouse; C516138:dorsomorphin; D000620:Aminoimidazole Carboxamide; D015256:Coenzyme A-Transferases; D003066:Coenzyme A Ligases; C023747:acetoacetyl-CoA synthetase; C031143:AICA ribonucleotide