Metabolic control by S6 kinases depends on dietary lipids

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

doi:10.1371/journal.pone.0032631

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Metabolic control by S6 kinases depends on dietary lipids

Journal article

Open access

Peer reviewed

Metabolic control by S6 kinases depends on dietary lipids

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, …

PloS one, Vol.7(3), pp.e32631-e32631

2012

DOI: 10.1371/journal.pone.0032631

PMCID: PMC3296718

PMID: 22412899

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Abstract

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.

Dietary Fats - metabolism

Ribosomal Protein S6 Kinases - metabolism

Amino Acids, Branched-Chain - metabolism

Cholesterol - blood

Diet, High-Fat - adverse effects

Male

Muscle, Skeletal - metabolism

Obesity - genetics

Ribosomal Protein S6 Kinases - deficiency

Fatty Acids, Nonesterified - metabolism

Glucose Intolerance - prevention & control

Leptin - blood

Gene Deletion

Female

Lipid Metabolism - genetics

Fatty Acids - metabolism

Cell Line

Glucose Intolerance - genetics

Mice, Knockout

Obesity - metabolism

Phenotype

Animals

Triglycerides - blood

Mice

Enzyme Activation

Ribosomal Protein S6 Kinases - genetics

Details

Title: Subtitle: Metabolic control by S6 kinases depends on dietary lipids
Creators: Tamara R Castañeda - Institute for Clinical Biochemistry and Pathobiochemistry, German Diabetes Center, Düsseldorf, Germany
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
Resource Type: Journal article
Publication Details: PloS one, Vol.7(3), pp.e32631-e32631
DOI: 10.1371/journal.pone.0032631
PMID: 22412899
PMCID: PMC3296718
NLM abbreviation: PLoS One
ISSN: 1932-6203
eISSN: 1932-6203
Publisher: Public Library of Science; United States
Grant note: DK056863 / NIDDK NIH HHS DK73802 / NIDDK NIH HHS R01 DK077975 / NIDDK NIH HHS DK078019 / NIDDK NIH HHS R01 DK078019 / NIDDK NIH HHS P01 DK056863 / NIDDK NIH HHS DK077975 / NIDDK NIH HHS R01 DK073802 / NIDDK NIH HHS
Language: English
Date published: 2012
Academic Unit: Iowa Neuroscience Institute; Neuroscience and Pharmacology; Internal Medicine
Record Identifier: 9984040319502771

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