concomitant down-regulation of Sodium laureth sulfate site PDHK-2 and lipase activity. To identify which lipase might be involved in mediating fat catabolism in response to dauer state duration, we examined the expression of eight currently identified and predicted lipases. We found highly induced expression of ATGL, HSL, and C07E3.9 PDHK-2 and Fat Consumption in C. elegans Survival a 15% survival rate when worms were subjected to 1% SDS treatment. Thus, PDHK-2 overexpression caused both an increase in lipase expression and abnormal dauer formation, although the relationship between these two events is not clear at present. It is also not clear whether overexpression of PDHK-2 caused the activation of lipases that consequently led to this aberrant dauer formation and lifecycle. Discussion On the basis of the results presented here, we propose the following metabolic axis: PDHK-2 deficiencyRdecreased lipasemediated fat consumptionRincreased survival rate under adverse nutritional conditions. This hypothesized relationship highlights an important regulatory role for PDHK-2 in starvation and the dauer state, where the glycolytic pathway has been shown to be less active, resulting in the greater availability of free fatty acids as fuel. Considered in this context, our results suggest that, as long as the glycolytic pathway is active, fatty acid mobilization does not take place; accordingly, PDHK-2 would not appear to play any role under these circumstances. Our data also show that PDHK-2 deficiency caused a decrease in ATGL, HSL and C07E3.9, consistent PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19828152 with this previous report. Thus, it is reasonable to speculate that the neuronal localization of PDHK-2 may be linked to metabolic control through the nervous system. In addition, PDHK-2 localization appears to be highly induced in muscle when worms are in starvation condition. Muscle is one of the most energy consuming tissues which contain highest number of mitochondria. However, we could not find any clear evidence as to the correlation with PDHK-2 and mitochondrial localization. It is also possible that posttranslational modifications of PDHK-2 could change the localization of this enzyme according to the nutritional state. For example, the wellfed condition causes activation of IIS, which might consequently phosphorylate PDHK-2 or its binding proteins, leading to different localization of this protein. A characteristic morphological feature of dauer larvae is the presence of high-density fat granules in the intestine, which are very important for long-term survival during the dauer stage. Although studies have shown that L2 worms store fats before entering the dauer state in order to survive, how mobilization of these fats is regulated during this dormant period remains largely PDHK-2 and Fat Consumption in C. elegans Survival unknown. Since fat utilization is critical for long-term survival during the dauer state or starvation, our data suggest that PDHK2 may be involved in the fine-tuning of fat consumption by modulating lipase expression specifically in response to the adverse nutritional conditions, in which IIS and TGF-b signaling are inactive but DAF-16 is active. That is, under well-fed conditions, PDHK-2 activity does not seem to influence lifespan and fat content, regardless of the 
activity of major signaling pathways or effecter molecules. However, with long-term starvation or in the dauer state, DAF-16 and NHR-49 apparently work to up-regulate PDHK-2, which consequently stimulates major lipa