Assessment of the aging of the brown adipose tissue by18F-FDG PET/CT imaging in the progeria mouse model LmnaG609G/G609G

ABSTRACT Brown adipose tissue (BAT) is an important energy metabolic organ that is closely related to obesity, type 2 diabetes, and atherosclerosis. Aging is one of the most important determinants of BAT activity. In this study, we used 18 F-FDG PET/CT imaging to assess the aging of the BAT in Lmna G609G/G609G mice. To evaluate the BAT activity, Lmna G609G/G609G and wild-type (WT) mice were injected with 18F-FDG, and PET/CT imaging was performed. The maximum standardized uptake value (SUV Max ) of the BAT was measured and the target/nontarget (T/NT) values of BAT were calculated. The transcription and the protein expression levels of the uncoupling protein 1 (UCP1), beta3-adrenergic receptor (β3-AR), and the PRdomain-containing16 (PRDM16), were measured by quantitative real-time polymerase chain reaction (RT-PCR) and Western blotting or immunohistochemical analysis. Apoptosis and cell senescence of the BAT, in WT and Lmna G609G/G609G mice, was detected by Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), and by CDKN2A/p16INK4a immunohistochemical staining, respectively. At 14 weeks of age, the BAT SUV Max and the expression levels of UCP1, β3-AR and PRDM16 in Lmna G609G/G609G mice was significantly lower than that in WT mice. At the same time, the number of p16INK4a and TUNEL positively stained cells (%) increased in Lmna G609G/G609G mice. Lmna G609G/G609G mice are an ideal model for studying BAT aging. The aging characteristics and the aging mechanism of BAT in Lmna G609G/G609G mice can mimic normal BAT aging.