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In  Caenorhabditis elegans , slow fat consumption has been suggested to contribute to the extension of the survival rate during nutritionally adverse conditions. Here, we investigated the potential role of pyruvate dehydrogenase kinase (PDHK)-2, the  C. elegans  homolog of mammalian PDK, effects on fat metabolism under nutritional conditions. PDHK-2 was expressed at low levels under well-fed conditions but was highly induced during long-term starvation and in the dauer state. This increase in  pdhk-2  expression was regulated by both DAF-16 and NHR-49. Dauer-specific induction of PDHK-2 was abolished upon entry into the post-dauer stage. Interestingly, in the long-term dauer state, stored fat levels were higher in  daf-2(e1370);pdhk-2  double mutants than in  daf-2(e1370) , suggesting a positive relationship between PDHK-2 activity and fat consumption. PDHK-2 deficiency has been shown to lead to greater preservation of residual fats, which would be predicted to contribute to survival during the dauer state. A test of this prediction showed that the survival rates of  daf-2(e1370);pdhk-2(tm3075)  and  daf-2(e1370);pdhk-2(tm3086)  double mutants were higher than that of  daf-2(e1370) , suggesting that loss of either the ATP-binding domain  (tm3075)  or branched chain keto-acid dehydrogenase kinase domain  (tm3086)  of PDHK-2 leads to reduced fat consumption and thus favors increased dauer survival. This attenuated fat consumption in the long-term dauer state of  C. elegans daf-2 (e1370);pdhk-2  mutants was associated with concomitant down-regulation of the lipases ATGL (adipose triglyceride lipase), HSL (hormone-sensitive lipase), and C07E3.9 (phospholipase). In contrast, PDHK-2 overexpression in wild-type starved worms induced lipase expression and promoted abnormal dauer formation. Thus, we propose that PDHK-2 serves as a molecular bridge, connecting fat metabolism and survival under nutritionally adverse conditions in  C. elegans .

PDHK-2 Deficiency Is Associated with Attenuation of Lipase-Mediated Fat Consumption for the Increased Survival of Caenorhabditis elegans Dauers