title: Deficiency of the transcriptional repressor B cell lymphoma 6 (Bcl6) is accompanied by dysregulated lipid metabolism.
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.
authors.affiliation: Department of Molecular & Integrative Physiology, Univ Michigan, Ann Arbor, Michigan, United States of America.
authors.forename: Christopher R
authors.initials: CR
authors.lastname: LaPensee
authors.affiliation: Graduate Program in Cellular & Molecular Biology, Univ Michigan, Ann Arbor, Michigan, United States of America.
authors.forename: Grace
authors.initials: G
authors.lastname: Lin
authors.affiliation: Dept of Microbiology & Immunology, Indiana Univ School of Medicine, Indianapolis, Indiana, United States of America.
authors.forename: Alexander L
authors.initials: AL
authors.lastname: Dent
authors.affiliation: Department of Molecular & Integrative Physiology, Univ Michigan, Ann Arbor, Michigan, United States of America; Graduate Program in Cellular & Molecular Biology, Univ Michigan, Ann Arbor, Michigan, United States of America.
authors.forename: Jessica
authors.initials: J
authors.lastname: Schwartz
mesh_terms: D000273:Adipose Tissue / Q000473:pathology; D000818:Animals; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D004268:DNA-Binding Proteins / Q000172:deficiency* / Q000378:metabolism; D005215:Fasting / Q000097:blood; D005227:Fatty Acids / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D050356:Lipid Metabolism / Q000235:genetics; D050155:Lipogenesis / Q000235:genetics; D008099:Liver / Q000378:metabolism; D008297:Male; D055442:Metabolome / Q000235:genetics; D018345:Mice, Knockout; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D009929:Organ Size; D010084:Oxidation-Reduction; D051560:Proto-Oncogene Proteins c-bcl-6; D012097:Repressor Proteins / Q000172:deficiency* / Q000378:metabolism; D044967:Serum / Q000378:metabolism; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D014280:Triglycerides / Q000378:metabolism
chemical_list: D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; C490010:Bcl6 protein, mouse; D004268:DNA-Binding Proteins; D005227:Fatty Acids; C506001:Mlxipl protein, mouse; D009687:Nuclear Proteins; D051560:Proto-Oncogene Proteins c-bcl-6; D012097:Repressor Proteins; C491409:Socs2 protein, mouse; D050826:Suppressor of Cytokine Signaling Proteins; D014157:Transcription Factors; D014280:Triglycerides