Role of lipid metabolism (WP2915)

"Lipases regulate life span in C. elegans. Several lipases, K04A8.5, LIPS-7, FIL-1, FIL-2, and ATGL-1, have been demonstrated to influence the lifespan of C. elegans. The figure depicts the mechanisms by which these lipases are regulated and the pathways by which they affect longevity. Well fed animals were shown to live longer during germline stem cell (GSC) arrest. This phenotype depends on K04A8.5 lipase activity, which was suggested to be promoted by the KRI-1/DAF-16 signalling pathway. Additionally, a ctbp-1 mutant also displayed increased lifespan during well fed conditions. It was proposed that this NAD(H)-dependent corepressor, CTBP-1, acted downstream of SIR2.1 and DAF-2 but up stream of DAF-16. One of its target genes lips-7 encodes a lipase and is required for the increased life span of ctbp-1 mutants. IRE-1 and HSP-4, which are normally involved in the unfolded protein response, are required for expression of FIL-1 and FIL-2 during starvation. The two transcription regulators, SBP-1 and CBP-1, are likewise required for FIL-1 and FIL-2 induction. The a2 catalytic subunit of AMP-dependent kinase (AMPK) regulates the activity of the C. elegans paralogue of the adipose triglyceride lipase, ATGL-1, during the dauer stage. AMPK is regulated by AMP levels and by phosphorylation by human homologue of LKB1 kinase PAR-4." Fig 1. Elle, et al., 2010. Fat storage genes identified in McKay et al., 2003.

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