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Control of hypothalamic malonyl‐CoA by central glucose and leptin
Author(s) -
Lane M. Daniel,
Wolfgang Michael,
Cha Seung Hun
Publication year - 2008
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.22.1_supplement.116.2
Subject(s) - medicine , endocrinology , leptin , ampk , malonyl coa , acetyl coa carboxylase , hypothalamus , carbohydrate metabolism , neuropeptide y receptor , chemistry , protein kinase a , metabolism , pyruvate carboxylase , phosphorylation , biology , beta oxidation , neuropeptide , enzyme , biochemistry , receptor , obesity
We investigated the responses of intermediates of the hypothalamic malonyl‐CoA signaling pathway to glucose and leptin. Hypothalamic malonyl‐CoA increases in proportion to the carbohydrate content of the diet consumed following food deprivation. After refeeding or peripheral glucose administration, blood glucose and hypothalamic malonyl‐CoA levels peak at 30 and 60 minutes, respectively. The malonyl‐CoA response depends on the amount of glucose administered and is blocked by the icv administration of an inhibitor of glucose metabolism, 2‐deoxyglucose (2‐DG). The change in hypothalamic malonyl‐CoA following glucose administration coincides with the suppression of phosphorylation of AMP kinase (AMPK) and acetyl‐CoA carboxylase. Blockade of glucose utilization in the CNS by icv 2‐DG prevented the effects of glucose on AMPK phosphorylation, malonyl‐CoA and neuropeptide expression in the hypothalamus and on food intake. Icv leptin increased hypothalamic malonyl‐CoA additively with glucose administration. Since leptin‐deficient ob/ob mice showed no defect in the glucose‐ or refeeding‐induced rise in hypothalamic malonyl‐CoA after food deprivation, it is evident that leptin is not required for this effect.