The DOI matches its Crossref record; 59 of the 59 references it cites were found in a registry or an index.
Elevated sensitivity to diet-induced obesity and insulin resistance in mice lacking 4E-BP1 and 4E-BP2
Open accessAbstract
The most common pathology associated with obesity is insulin resistance, which results in the onset of type 2 diabetes mellitus. Several studies have implicated the mammalian target of rapamycin (mTOR) signaling pathway in obesity. Eukaryotic translation initiation factor 4E-binding (eIF4E-binding) proteins (4E-BPs), which repress translation by binding to eIF4E, are downstream effectors of mTOR. We report that the combined disruption of 4E-BP1 and 4E-BP2 in mice increased their sensitivity to diet-induced obesity. Increased adiposity was explained at least in part by accelerated adipogenesis driven by increased expression of CCAAT/enhancer-binding protein delta (C/EBPdelta), C/EBPalpha, and PPARgamma coupled with reduced energy expenditure, reduced lipolysis, and greater fatty acid reesterification in the adipose tissue of 4E-BP1 and 4E-BP2 double KO mice. Increased insulin resistance in 4E-BP1 and 4E-BP2 double KO mice was associated with increased ribosomal protein S6 kinase (S6K) activity and impairment of Akt signaling in muscle, liver, and adipose tissue. These data clearly demonstrate the role of 4E-BPs as a metabolic brake in the development of obesity and reinforce the idea that deregulated mTOR signaling is associated with the development of the metabolic syndrome.
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Cites
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Self-citationPPARγ Is Required for the Differentiation of Adipose Tissue In Vivo and In Vitro
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Absence of S6K1 protects against age- and diet-induced obesity while enhancing insulin sensitivity
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Self-citation
Cited by
mTOR Signaling in Growth Control and Disease
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mTOR: from growth signal integration to cancer, diabetes and ageing
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Self-citationCornier, M.-A., Dabelea, D., Hernandez, T. L., Lindstrom, R. C., Steig, A. J., Stob, N. R., Van Pelt, R. E., Wang, H., & Eckel, R. H. (2008) · Endocrine Reviews · doi:10.1210/er.2008-0024 · Cited by 2,162
Mechanisms regulating skeletal muscle growth and atrophy
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Metadata
- Authors
- Le Bacquer, O., Petroulakis, E., Paglialunga, S., Poulin, F., Richard, D., Cianflone, K., & Sonenberg, N.
- Venue
- Journal of Clinical Investigation
- Published
- 2007-02-01
- Volume
- 117
- Issue
- 2
- Pages
- 387-396
- ISSN
- 0021-9738 (ISSN-L)
- OpenAlex
- W2087962053
- Cited by
- 334
- References
- 59
- FWCI
- 16.96
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Le Bacquer, O., Petroulakis, E., Paglialunga, S., Poulin, F., Richard, D., Cianflone, K., & Sonenberg, N. (2007). Elevated sensitivity to diet-induced obesity and insulin resistance in mice lacking 4E-BP1 and 4E-BP2. Journal of Clinical Investigation. https://doi.org/10.1172/jci29528
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