Absence of S6K1 protects against age- and diet-induced obesity while enhancing insulin sensitivity

By S. Um, F. Frigerio, Mitsuhiro Watanabe, F. Picard, M. Joaquin, Melanie Sticker, S. Fumagalli, P. Allegrini, S. Kozma, Johan Auwerx and 1 more. Nature, 2004

1,741 citations recorded by the source corpus.

Subfields: Molecular Biology, Physiology

View Paper: https://www.semanticscholar.org/paper/42682f41df62ed526553a8b1a9fbb784df9b6db2

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Citations in the corpus

PHLPP and a second isoform, PHLPP2, differentially attenuate the amplitude of Akt signaling by regulating distinct Akt isoforms. (2007, background): “A candidate for such feedback regulation is p70S6K, whose activation has been established to result in decreased phosphorylation and activation of Akt (Harrington et al., 2004; O’Reilly et al., 2006; Um et al., 2004).”
mTOR signaling in growth control and disease (2012, positive): “Although our understanding of the feedback loops from mTORC1 to RTK signaling has progressed, it is important to point out that formal evidence ismissing showing that the activation of feedback signaling by rapamycin and its derivates limits the therapeutic potential of these molecules.”
Tumor necrosis factor-alpha induces skeletal muscle insulin resistance in healthy human subjects via inhibition of Akt substrate 160 phosphorylation. (2005, background): “These targets have been implicated in the negative regulation of insulin signal transduction (24).”
mTOR: a pharmacologic target for autophagy regulation. (2015, positive): “Ribosomal protein S6 kinase 1 (S6K1), a downstream effector of mTORC1, negatively regulates the insulin receptor substrate 1 (IRS1), which is a positive mediator of RTK/PI3K signaling (51, 52).”
Dietary and genetic obesity promote liver inflammation and tumorigenesis by enhancing IL-6 and TNF expression (2010, background): “As expected (Tremblay et al., 2007; Um et al., 2004), obesity was associated with decreased AKT phosphorylation and increased phosphorylation of the mTOR target S6 kinase and its substrate ribosomal protein S6 (Figure 4A).”
Targeting phosphoinositide 3-kinase: moving towards therapy. (2008, background): “In contrast, S6K1 deficient mice are viable, but show developmental retardation, smaller pancreatic β-cell size, are hypoinsulinemic and are mildly glucose intolerant [42,168].”
Defining the role of mTOR in cancer. (2007, background): “Mice lacking s6k1 are viable, but when challenged with a high-fat diet, despite the 12 Cancer Cell 12, July 2007 ©2007 Elsevier Inc. fact that insulin receptors become desensitized, they are resistant to obesity because loss of the feedback loop enhances their insulin sensitivity (Um et al., 2004).”
The Human Obesity Gene Map: The 2005 Update (2006, background): “2 RPS6KB1 Ribosomal protein S6 kinase, polypeptide 1, S6K1 Resistant to diet-induced obesity (543)”