In this proposal we will use mouse models that have mutations in the Cdk4 locus. Cdk4-/- mice are diabetic and lean, and in contrast, Cdk4R24C mice are non-diabetic and heavier. These observations are consistent with a role of the RB/E2F pathway in adipogenesis amd muscle differentiation. We hypothesize that Cdk4 activity may regulate adipogenesis and muscle development and function, and, by extension, overall energy balance. We are studying mechanisms of glucose tolerance and energy homeostasis by evaluating CDk4-dependent functions in different metabolic organs in the Cdk4 mice. The findings are revealing important role of Cdk4 in processes that modulate energy balance.

Project Start
Project End
Budget Start
Budget End
Support Year
6
Fiscal Year
2012
Total Cost
$346,331
Indirect Cost
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State
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Yadav, Hariom; Rane, Sushil G (2015) Dietary fatty acids: Friends or foes? Obesity (Silver Spring) 23:1329
Tiano, Joseph P; Springer, Danielle A; Rane, Sushil G (2015) SMAD3 negatively regulates serum irisin and skeletal muscle FNDC5 and peroxisome proliferator-activated receptor γ coactivator 1-α (PGC-1α) during exercise. J Biol Chem 290:7671-84
Tarbell, Kristin V; Rane, Sushil G (2015) Saving β cell function in the NIK of time. J Exp Med 212:1140-1
Fernandez, Patricia; Scaffidi, Paola; Markert, Elke et al. (2014) Transformation resistance in a premature aging disorder identifies a tumor-protective function of BRD4. Cell Rep 9:248-60
Yadav, Hariom; Lee, Ji-Hyeon; Lloyd, John et al. (2013) Beneficial Metabolic Effects of a Probiotic via Butyrate-induced GLP-1 Hormone Secretion. J Biol Chem 288:25088-97
Jiao, W; Lin, H-M; Datta, J et al. (2008) Aberrant nucleocytoplasmic localization of the retinoblastoma tumor suppressor protein in human cancer correlates with moderate/poor tumor differentiation. Oncogene 27:3156-64