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Ketone body utilization is regulated by leptin signaling in hypothalamic neuron
Author(s) -
Yamasaki Masahiro,
Hasegawa Shinya,
Narishima Ryota,
Fukui Tetsuya
Publication year - 2011
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.25.1_supplement.920.9
Subject(s) - leptin , hypothalamus , endocrinology , medicine , ampk , activator (genetics) , chemistry , central nervous system , adipose tissue , biology , enzyme , obesity , biochemistry , protein kinase a , receptor
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 and ventromedial hypothalamic nucleus in hypothalamus but not in other brain regions. Moreover, Leptin increased AACS mRNA level both in primary mouse neural cells and in neural cell line (N41). In N41 cells, AACS level was decreased by AMPK activator (AICAR) but increased by its inhibitor (compound C). 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.