Brown adipose YY1 deficiency activates expression of secreted proteins linked to energy expenditure and prevents diet-induced obesity

Francisco Verdeguer, Meghan S. Soustek, Maximilian Hatting, Sharon M. Blättler, Devin McDonald, Joeva J. Barrow, Pere Puigserver

Research output: Contribution to journalArticle

Abstract

Mitochondrial oxidative and thermogenic functions in brown and beige adipose tissues modulate rates of energy expenditure. It is unclear, however, how beige or white adipose tissue contributes to brown fat thermogenic function or compensates for partial deficiencies in this tissue and protects against obesity. Here, we show that the transcription factor Yin Yang 1 (YY1) in brown adipose tissue activates the canonical thermogenic and uncoupling gene expression program. In contrast, YY1 represses a series of secreted proteins, including fibroblast growth factor 21 (FGF21), bone morphogenetic protein 8b (BMP8b), growth differentiation factor 15 (GDF15), angiopoietin-like 6 (Angptl6), neuromedin B, and nesfatin, linked to energy expenditure. Despite substantial decreases in mitochondrial thermogenic proteins in brown fat, mice lacking YY1 in this tissue are strongly protected against diet-induced obesity and exhibit increased energy expenditure and oxygen consumption in beige and white fat depots. The increased expression of secreted proteins correlates with elevation of energy expenditure and promotion of beige and white fat activation. These results indicate that YY1 in brown adipose tissue controls antagonistic gene expression programs associated with energy balance and maintenance of body weight.

Original languageEnglish (US)
Pages (from-to)184-196
Number of pages13
JournalMolecular and Cellular Biology
Volume36
Issue number1
DOIs
StatePublished - 2016
Externally publishedYes

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Yang Deficiency
Yin-Yang
Brown Adipose Tissue
Energy Metabolism
Obesity
White Adipose Tissue
Diet
Proteins
Growth Differentiation Factor 15
Angiopoietins
Gene Expression
Bone Morphogenetic Proteins
Mitochondrial Proteins
Oxygen Consumption
Transcription Factors
Beige Adipose Tissue

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Verdeguer, F., Soustek, M. S., Hatting, M., Blättler, S. M., McDonald, D., Barrow, J. J., & Puigserver, P. (2016). Brown adipose YY1 deficiency activates expression of secreted proteins linked to energy expenditure and prevents diet-induced obesity. Molecular and Cellular Biology, 36(1), 184-196. https://doi.org/10.1128/MCB.00722-15

Brown adipose YY1 deficiency activates expression of secreted proteins linked to energy expenditure and prevents diet-induced obesity. / Verdeguer, Francisco; Soustek, Meghan S.; Hatting, Maximilian; Blättler, Sharon M.; McDonald, Devin; Barrow, Joeva J.; Puigserver, Pere.

In: Molecular and Cellular Biology, Vol. 36, No. 1, 2016, p. 184-196.

Research output: Contribution to journalArticle

Verdeguer, F, Soustek, MS, Hatting, M, Blättler, SM, McDonald, D, Barrow, JJ & Puigserver, P 2016, 'Brown adipose YY1 deficiency activates expression of secreted proteins linked to energy expenditure and prevents diet-induced obesity', Molecular and Cellular Biology, vol. 36, no. 1, pp. 184-196. https://doi.org/10.1128/MCB.00722-15
Verdeguer, Francisco ; Soustek, Meghan S. ; Hatting, Maximilian ; Blättler, Sharon M. ; McDonald, Devin ; Barrow, Joeva J. ; Puigserver, Pere. / Brown adipose YY1 deficiency activates expression of secreted proteins linked to energy expenditure and prevents diet-induced obesity. In: Molecular and Cellular Biology. 2016 ; Vol. 36, No. 1. pp. 184-196.
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