Metabolic control by S6 kinases depends on dietary lipids.
Targeted deletion of S6 kinase (S6K) 1 in mice leads to higher energy expenditure and improved glucose metabolism. However, the molecular mechanisms controlling these effects remain to be fully elucidated. Here, we analyze the potential role of dietary lipids in regulating the mTORC1/S6K system. Ana...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2012-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3296718?pdf=render |
| _version_ | 1818404754952290304 |
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| author | Tamara R Castañeda William Abplanalp Sung Hee Um Paul T Pfluger Brigitte Schrott Kimberly Brown Erin Grant Larissa Carnevalli Stephen C Benoit Donald A Morgan Dean Gilham David Y Hui Kamal Rahmouni George Thomas Sara C Kozma Deborah J Clegg Matthias H Tschöp |
| author_facet | Tamara R Castañeda William Abplanalp Sung Hee Um Paul T Pfluger Brigitte Schrott Kimberly Brown Erin Grant Larissa Carnevalli Stephen C Benoit Donald A Morgan Dean Gilham David Y Hui Kamal Rahmouni George Thomas Sara C Kozma Deborah J Clegg Matthias H Tschöp |
| author_sort | Tamara R Castañeda |
| collection | DOAJ |
| description | Targeted deletion of S6 kinase (S6K) 1 in mice leads to higher energy expenditure and improved glucose metabolism. However, the molecular mechanisms controlling these effects remain to be fully elucidated. Here, we analyze the potential role of dietary lipids in regulating the mTORC1/S6K system. Analysis of S6K phosphorylation in vivo and in vitro showed that dietary lipids activate S6K, and this effect is not dependent upon amino acids. Comparison of male mice lacking S6K1 and 2 (S6K-dko) with wt controls showed that S6K-dko mice are protected against obesity and glucose intolerance induced by a high-fat diet. S6K-dko mice fed a high-fat diet had increased energy expenditure, improved glucose tolerance, lower fat mass gain, and changes in markers of lipid metabolism. Importantly, however, these metabolic phenotypes were dependent upon dietary lipids, with no such effects observed in S6K-dko mice fed a fat-free diet. These changes appear to be mediated via modulation of cellular metabolism in skeletal muscle, as shown by the expression of genes involved in energy metabolism. Taken together, our results suggest that the metabolic functions of S6K in vivo play a key role as a molecular interface connecting dietary lipids to the endogenous control of energy metabolism. |
| first_indexed | 2024-12-14T08:45:11Z |
| format | Article |
| id | doaj.art-7da010e228ee4cde9cfbd8ad394306a7 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-14T08:45:11Z |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-7da010e228ee4cde9cfbd8ad394306a72022-12-21T23:09:11ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0173e3263110.1371/journal.pone.0032631Metabolic control by S6 kinases depends on dietary lipids.Tamara R CastañedaWilliam AbplanalpSung Hee UmPaul T PflugerBrigitte SchrottKimberly BrownErin GrantLarissa CarnevalliStephen C BenoitDonald A MorganDean GilhamDavid Y HuiKamal RahmouniGeorge ThomasSara C KozmaDeborah J CleggMatthias H TschöpTargeted deletion of S6 kinase (S6K) 1 in mice leads to higher energy expenditure and improved glucose metabolism. However, the molecular mechanisms controlling these effects remain to be fully elucidated. Here, we analyze the potential role of dietary lipids in regulating the mTORC1/S6K system. Analysis of S6K phosphorylation in vivo and in vitro showed that dietary lipids activate S6K, and this effect is not dependent upon amino acids. Comparison of male mice lacking S6K1 and 2 (S6K-dko) with wt controls showed that S6K-dko mice are protected against obesity and glucose intolerance induced by a high-fat diet. S6K-dko mice fed a high-fat diet had increased energy expenditure, improved glucose tolerance, lower fat mass gain, and changes in markers of lipid metabolism. Importantly, however, these metabolic phenotypes were dependent upon dietary lipids, with no such effects observed in S6K-dko mice fed a fat-free diet. These changes appear to be mediated via modulation of cellular metabolism in skeletal muscle, as shown by the expression of genes involved in energy metabolism. Taken together, our results suggest that the metabolic functions of S6K in vivo play a key role as a molecular interface connecting dietary lipids to the endogenous control of energy metabolism.http://europepmc.org/articles/PMC3296718?pdf=render |
| spellingShingle | Tamara R Castañeda William Abplanalp Sung Hee Um Paul T Pfluger Brigitte Schrott Kimberly Brown Erin Grant Larissa Carnevalli Stephen C Benoit Donald A Morgan Dean Gilham David Y Hui Kamal Rahmouni George Thomas Sara C Kozma Deborah J Clegg Matthias H Tschöp Metabolic control by S6 kinases depends on dietary lipids. PLoS ONE |
| title | Metabolic control by S6 kinases depends on dietary lipids. |
| title_full | Metabolic control by S6 kinases depends on dietary lipids. |
| title_fullStr | Metabolic control by S6 kinases depends on dietary lipids. |
| title_full_unstemmed | Metabolic control by S6 kinases depends on dietary lipids. |
| title_short | Metabolic control by S6 kinases depends on dietary lipids. |
| title_sort | metabolic control by s6 kinases depends on dietary lipids |
| url | http://europepmc.org/articles/PMC3296718?pdf=render |
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