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Fatty Acid Metabolism, the Central Nervous System, and Feeding
Author(s) -
Ronnett Gabriele V.,
Kleman Amy M.,
Kim EunKyoung,
Landree Leslie E.,
Tu Yajun
Publication year - 2006
Publication title -
obesity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.438
H-Index - 199
eISSN - 1930-739X
pISSN - 1930-7381
DOI - 10.1038/oby.2006.309
Subject(s) - cerulenin , fatty acid synthase , fatty acid synthesis , beta oxidation , orexigenic , fatty acid metabolism , ampk , malonyl coa , fatty acid , biochemistry , chemistry , carnitine , metabolism , protein kinase a , biology , endocrinology , enzyme , neuropeptide , neuropeptide y receptor , receptor
A potential role for fatty acid metabolism in the regulation of energy balance in the brain or in the periphery has been considered only recently. Fatty acid synthase (FAS) catalyzes the synthesis of long‐chain fatty acids, whereas the breakdown of fatty acids by β‐oxidation is regulated by carnitine palmitoyltransferase‐1, the rate‐limiting enzyme for the entry of fatty acids into the mitochondria for oxidation. While the question of the physiological role of fatty acid metabolism remains to be resolved, studies indicate that inhibition of FAS or stimulation of carnitine palmitoyltransferase‐1 using cerulenin or synthetic FAS inhibitors reduces food intake and incurs profound and reversible weight loss. Several hypotheses regarding the mechanisms by which these small molecules mediate their effects have been entertained. Centrally, these compounds alter the expression of hypothalamic neuropeptides, generally reducing the expression of orexigenic peptides. Whether through central, peripheral, or combined central and peripheral mechanisms, these compounds also increase energy consumption to augment weight loss. In vitro and in vivo studies indicate that at least part of C75's effects is mediated by modulation of adenosine monophosphate‐activated protein kinase, a member of an energy‐sensing kinase family. These compounds, with chronic treatment, also alter gene expression peripherally to favor a state of enhanced energy consumption. Together, these effects raise the possibility that pharmacological alterations in fatty acid synthesis/degradation may serve as a target for obesity therapeutics.