Tagln1-Cre driven Ercc1 deficiency reveals sex specific effects on adipose tissue in mice.

Metabolic aging is marked by changes in insulin sensitivity and adipose tissue remodeling, including the vasculature. Transgelin 1 (Tagln1), a marker for vascular smooth muscle cells (VSMC), is used as a promoter for Cre-driven gene knockout (KO) in mice. However, Tagln1 is also expressed in white adipocytes. We previously showed that Tagln1-Cre driven KO of DNA repair endonuclease Ercc1 in mice (Tagln1-Cre Ercc1 mice) leads to accelerated aging of VSMC and perivascular adipocytes resulting in vascular dysfunction and lipodystrophic-like perivascular adipose tissue. The aim of this study was to investigate the consequences of Tagln1-driven Ercc1 deficiency on whole body metabolism and adipose tissue morphology and function. Tagln1-Cre Ercc1 mice did not show the usual age-related gain in fat mass. Adipose tissue depots from male Tagln1-Cre Ercc1 mice shared similarities with adipose tissue depots from advanced aged mice including smaller white adipocyte size, decreased vascularization, increased oxidative stress, macrophage infiltration and fibrosis compared to male WT mice. Female Tagln1-Cre Ercc1 mice showed an upregulation of antioxidant genes which might be a protective response resulting in minor changes in their adipose tissue depots compared to female WT mice. Male Tagln1-Cre Ercc1 mice showed partially preserved adipose tissue function and improved insulin sensitivity. Interestingly, analyses showed that Tagln1 expression varied sex- and adipose tissue depot-specific in WT mice. To conclude, we showed that accelerated aging induced by Ercc1-deficiency in Tagln-1 dependent cell populations leads to WAT and BAT remodeling and inflammation as also observed in normal aging.