Loss of Transcriptional Repression by BCL6 Confers Insulin Sensitivity in the Setting of Obesity

Madhavi D. Senagolage, Meredith A. Sommars, Krithika Ramachandran, Christopher R. Futtner, Yasuhiro Omura, Amanda L. Allred, Jianing Wang, Cynthia Yang, Daniele Procissi, Ronald M. Evans, Xianlin Han, Ilya R. Bederman, Grant D. Barish

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

Accumulation of visceral adiposity is directly linked to the morbidity of obesity, while subcutaneous body fat is considered more benign. We have identified an unexpected role for B cell lymphoma 6 (BCL6), a critical regulator of immunity, in the developmental expansion of subcutaneous adipose tissue. In adipocyte-specific knockout mice (Bcl6AKO), we found that Bcl6 deletion results in strikingly increased inguinal, but not perigonadal, adipocyte size and tissue mass in addition to marked insulin sensitivity. Genome-wide RNA expression and DNA binding analyses revealed that BCL6 controls gene networks involved in cell growth and fatty acid biosynthesis. Using deuterium label incorporation and comprehensive adipokine and lipid profiling, we discovered that ablation of adipocyte Bcl6 enhances subcutaneous adipocyte lipogenesis, increases levels of adiponectin and fatty acid esters of hydroxy fatty acids (FAHFAs), and prevents steatosis. Thus, our studies identify BCL6 as a negative regulator of subcutaneous adipose tissue expansion and metabolic health.

Original languageEnglish (US)
Pages (from-to)3283-3298.e6
JournalCell Reports
Volume25
Issue number12
DOIs
StatePublished - Dec 18 2018

Keywords

  • BCL-6
  • BCL6
  • FAHFA
  • PAHSA
  • adipocyte
  • adiponectin
  • adipose tissue
  • ceramide
  • fatty acid esters of hydroxy fatty acids
  • hypertrophy
  • insulin sensitivity
  • lipogenesis
  • obesity
  • repressor
  • subcutaneous fat

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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  • Cite this

    Senagolage, M. D., Sommars, M. A., Ramachandran, K., Futtner, C. R., Omura, Y., Allred, A. L., Wang, J., Yang, C., Procissi, D., Evans, R. M., Han, X., Bederman, I. R., & Barish, G. D. (2018). Loss of Transcriptional Repression by BCL6 Confers Insulin Sensitivity in the Setting of Obesity. Cell Reports, 25(12), 3283-3298.e6. https://doi.org/10.1016/j.celrep.2018.11.074