The evolutionarily conserved AMP-activated protein kinase (AMPK) is a critical energy sensor in eukaryotes. In general, upregulation of AMPK leads to shutting down energy consuming processes and activation of energy generating processes. In C. elegans, the catalytic alpha subunit, encoded by
aak-2, has been shown to have roles in regulating fat storage during the hibernating dauer state as well as longevity in both dauer and non-dauer animals.1,2 We found that
aak-2 deficient animals have increased feeding rate relative to wild type animals, and reconstitution studies suggest that expression in pharyngeal muscle and the nervous system is sufficient for restoration of wild type feeding rate to
aak-2 mutant animals. Moreover, using various neuron specific promoters, we found that neural sufficiency of
aak-2 for feeding regulation can be restricted to the small subset of neurons defined by an
hlh-34 promoter. Interestingly,
hlh-34 encodes for a basic helix-loop-helix transcription factor whose mammalian counterpart,
sim-1, has known developmental and regulatory roles in specific regions of the hypothalamus. Mammals deficient in SIM-1 develop obesity and exhibit increased feeding behavior.3 Thus, the role of AAK-2 in
hlh-34/sim-1 expressing cells in modulating metabolism and feeding behavior may be conserved across evolution. References: 1 Narbonne, P. and Roy R., 2009. Nature. 457, 210-213. 2 Apfeld, J., O'Connor, G, McDonagh, T., DiStefano, P.S., Curtis, R., 2004. Genes and Dev. 18, 3004-3009. 3 Michaud, J.L., Boucher, F., Melnyk A., Gauthier, F., Goshu, E., Levy, E., Mitchell, G.A., Himms-Hagen, J., Fan, C.M., 2001. Hum. Mol. Genet. 10, 1465-73.