Deficiency of the transcriptional repressor B cell lymphoma 6 (Bcl6) is accompanied by dysregulated lipid metabolism

Christopher R. LaPensee, Grace Lin, Alexander Dent, Jessica Schwartz

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

The transcriptional repressor B-cell Lymphoma 6 (Bcl6) was recently identified in a profile of genes regulated in adipocytes, suggesting a relationship between Bcl6 and metabolic regulation. As a representative target gene repressed by Bcl6, Suppressor of Cytokine Signaling (Socs) 2 expression was elevated in Bcl6 deficient (KO) mice, including metabolic tissues liver, adipose tissue and muscle, as well as in spleen and thymus. Bcl6 occupied the Socs2 promoter in wild-type, but not Bcl6 KO mice, suggesting direct regulation of Socs2 by Bcl6 in vivo. Mice deficient in Bcl6 were found to exhibit multiple features of dysregulated lipid metabolism. Adipose tissue mass was dramatically reduced or absent in Bcl6 KO mice. Further, hepatic and serum triglycerides were low. Bcl6 deficiency was accompanied by decreased hepatic expression of Stearoyl-CoA desaturase 1 (Scd1) and Fatty acid synthase (Fasn) genes which encode lipogenic enzymes. Expression of the gene for the transcription factor Carbohydrate-Responsive Element Binding Protein (Chrebp), which regulates expression of lipogenic genes, was also reduced in liver of Bcl6 KO mice. Bcl6 deficiency disrupted fasting-induced increases in hepatic triglyceride deposition, but not decreases in lipogenic gene expression. Taken together, these findings suggest that in addition to its well-recognized roles in immune regulation, Bcl6 plays a role in regulatory events of lipid metabolism, and that in the absence of Bcl6, lipid metabolism in liver and adipose tissue is dysregulated.

Original languageEnglish
Article numbere97090
JournalPLoS One
Volume9
Issue number6
DOIs
StatePublished - Jun 3 2014

Fingerprint

B-Cell Lymphoma
lymphoma
Lipid Metabolism
lipid metabolism
B-lymphocytes
Genes
Cells
Liver
Tissue
Triglycerides
Stearoyl-CoA Desaturase
liver
Thymus
Fatty Acid Synthases
mice
adipose tissue
Gene expression
Adipose Tissue
Muscle
Carrier Proteins

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Deficiency of the transcriptional repressor B cell lymphoma 6 (Bcl6) is accompanied by dysregulated lipid metabolism. / LaPensee, Christopher R.; Lin, Grace; Dent, Alexander; Schwartz, Jessica.

In: PLoS One, Vol. 9, No. 6, e97090, 03.06.2014.

Research output: Contribution to journalArticle

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