PDHK-2 deficiency is associated with attenuation of lipase-mediated fat consumption for the increased survival of Caenorhabditis elegans dauers.
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...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2012-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3407204?pdf=render |
| _version_ | 1829494742075834368 |
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| author | Sunhee Kim E-Jin Shin Jeong-Hoon Hahm Pil-Jong Park Ji-Eun Hwang Young-Ki Paik |
| author_facet | Sunhee Kim E-Jin Shin Jeong-Hoon Hahm Pil-Jong Park Ji-Eun Hwang Young-Ki Paik |
| author_sort | Sunhee Kim |
| collection | DOAJ |
| description | 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. |
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| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-16T06:57:28Z |
| publishDate | 2012-01-01 |
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| spelling | doaj.art-99de48ec62c8473f823c48694f7fb9e12022-12-21T22:40:15ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0177e4175510.1371/journal.pone.0041755PDHK-2 deficiency is associated with attenuation of lipase-mediated fat consumption for the increased survival of Caenorhabditis elegans dauers.Sunhee KimE-Jin ShinJeong-Hoon HahmPil-Jong ParkJi-Eun HwangYoung-Ki PaikIn 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.http://europepmc.org/articles/PMC3407204?pdf=render |
| spellingShingle | Sunhee Kim E-Jin Shin Jeong-Hoon Hahm Pil-Jong Park Ji-Eun Hwang Young-Ki Paik PDHK-2 deficiency is associated with attenuation of lipase-mediated fat consumption for the increased survival of Caenorhabditis elegans dauers. PLoS ONE |
| title | PDHK-2 deficiency is associated with attenuation of lipase-mediated fat consumption for the increased survival of Caenorhabditis elegans dauers. |
| title_full | PDHK-2 deficiency is associated with attenuation of lipase-mediated fat consumption for the increased survival of Caenorhabditis elegans dauers. |
| title_fullStr | PDHK-2 deficiency is associated with attenuation of lipase-mediated fat consumption for the increased survival of Caenorhabditis elegans dauers. |
| title_full_unstemmed | PDHK-2 deficiency is associated with attenuation of lipase-mediated fat consumption for the increased survival of Caenorhabditis elegans dauers. |
| title_short | PDHK-2 deficiency is associated with attenuation of lipase-mediated fat consumption for the increased survival of Caenorhabditis elegans dauers. |
| title_sort | pdhk 2 deficiency is associated with attenuation of lipase mediated fat consumption for the increased survival of caenorhabditis elegans dauers |
| url | http://europepmc.org/articles/PMC3407204?pdf=render |
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