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 taken 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.In addition, we have screened the PGC-1alpha promoter to identify novel transcriptional pathways that turn on PGC-1alpha expression. We are currently validating the binding of these candidate factors and assessing the effects of their pharmachological activation on energy metabolism.

Project Start
Project End
Budget Start
Budget End
Support Year
7
Fiscal Year
2013
Total Cost
$494,071
Indirect Cost
City
State
Country
Zip Code
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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