Deletion of Trim28 in committed adipocytes promotes obesity but preserves glucose tolerance

The effective storage of lipids in white adipose tissue (WAT) critically impacts whole body energy homeostasis. Many genes have been implicated in WAT lipid metabolism, including tripartite motif containing 28 (Trim28), a gene proposed to primarily influence adiposity via epigenetic mechanisms in embryonic development. However, in the current study we demonstrate that mice with deletion of Trim28 specifically in committed adipocytes, also develop obesity similar to global Trim28 deletion models, highlighting a post-developmental role for Trim28. These effects were exacerbated in female mice, contributing to the growing notion that Trim28 is a sex-specific regulator of obesity. Mechanistically, this phenotype involves alterations in lipolysis and triglyceride metabolism, explained in part by loss of Klf14 expression, a gene previously demonstrated to modulate adipocyte size and body composition in a sex-specific manner. Thus, these findings provide evidence that Trim28 is a bona fide, sex specific regulator of post-developmental adiposity and WAT function.

Simon T. Bond, Emily J. King, Darren C. Henstridge, Adrian Tran, Sarah C. Moody, Christine Yang, Yingying Liu, Natalie A. Mellett, Artika P. Nath, Michael Inouye, Elizabeth J. Tarling, Thomas Q. de Aguiar Vallim, Peter J. Meikle, Anna C. Calkin, Brian G. Drew