The transcriptional coactivator PGC-1alpha plays a central role in lipid metabolism;although its specific regulatory functions have been extensively studied, not much is known about the identity of potential interacting molecules that could act as coregulators and switch on/off its activity in response to metabolic cues. We have undertaken a biochemical approach followed by mass spectrometry and recently characterized a novel PGC-1alpha binding molecule that is able to enhance PGC-1alpha's transcriptional activity in vitro. We are currently performing gain-and loss-of-function experiments assessing the effects of this novel cofactor on the expression of genes regulated by PGC-1alpha and we are determining its overall effects on lipid beta-oxidation in vivo.

Project Start
Project End
Budget Start
Budget End
Support Year
6
Fiscal Year
2012
Total Cost
$512,539
Indirect Cost
City
State
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Mueller, Elisabetta (2016) Browning and Graying: Novel Transcriptional Regulators of Brown and Beige Fat Tissues and Aging. Front Endocrinol (Lausanne) 7:19
Ma, Xinran; Xu, Lingyan; Mueller, Elisabetta (2016) Forkhead box A3 mediates glucocorticoid receptor function in adipose tissue. Proc Natl Acad Sci U S A 113:3377-82
Adler-Wailes, D C; Alberobello, A T; Ma, X et al. (2015) Analysis of variants and mutations in the human winged helix FOXA3 gene and associations with metabolic traits. Int J Obes (Lond) 39:888-92
Ma, Xinran; Xu, Lingyan; Alberobello, Anna Teresa et al. (2015) Celastrol Protects against Obesity and Metabolic Dysfunction through Activation of a HSF1-PGC1α Transcriptional Axis. Cell Metab :
Ma, Xinran; Xu, Lingyan; Mueller, Elisabetta (2015) Calorie hoarding and thrifting: Foxa3 finds a way. Adipocyte 4:325-8
Ma, Xinran; Xu, Lingyan; Gavrilova, Oksana et al. (2014) Role of forkhead box protein A3 in age-associated metabolic decline. Proc Natl Acad Sci U S A 111:14289-94
Park, Jun Hong; Kang, Hong Jun; Kang, Soo Im et al. (2013) A multifunctional protein, EWS, is essential for early brown fat lineage determination. Dev Cell 26:393-404
Mueller, Elisabetta (2013) Understanding the variegation of fat: Novel regulators of adipocyte differentiation and fat tissue biology. Biochim Biophys Acta :
Meruvu, Sunitha; Hugendubler, Lynne; Mueller, Elisabetta (2011) Regulation of adipocyte differentiation by the zinc finger protein ZNF638. J Biol Chem 286:26516-23
Teng, Ruifeng; Gavrilova, Oksana; Suzuki, Norio et al. (2011) Disrupted erythropoietin signalling promotes obesity and alters hypothalamus proopiomelanocortin production. Nat Commun 2:520

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