Abstract
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Purpose: Introduction 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. However, there is no suitable model available to study the BAT aging up to now. LmnaG609G/G609G mice was constructed and as the models of aging have been widely used in aging studies. In this study we assessed whether the progeria mouse model LmnaG609G/G609G is suitable for BAT aging research. 18F-FDG PET/CT imaging technique was used to qualitatively and quantitatively analyze the relationship between 18F-FDG PET/CT imaging and aging of BAT in LmnaG609G/G609G mice. The relationship between BAT-related molecular markers UCP1 and β3-AR levels and 18F-FDG uptake was examined. In addition, the mechanism of BAT dysfunction in mice was studied.
Methods: To evaluate the BAT activity, LmnaG609G/G609G and wild-type (WT) mice were injected with 18F-FDG, and PET/CT imaging was performed. The maximum standardized uptake value (SUVMax) of the BAT was measured and the target/nontarget (T/NT) values of BAT were calculated by defining the lung as a reference. 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 LmnaG609G/G609G mice, was detected by Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), and by CDKN2A/p16INK4a immunohistochemical staining, respectively.
Results: At 14 weeks of age, the BAT SUVMax, the T/NT ratio, and the expression levels of UCP1, β3-AR and PRDM16 in LmnaG609G/G609G mice was significantly lower than that in WT mice (Fig. 1, 2). At the same time, the number of p16INK4a and TUNEL positively stained cells (%) increased in LmnaG609G/G609G mice (Fig. 3).
Conclusions: LmnaG609G/G609G mice are an ideal model for studying BAT aging. The 18F-FDG uptake and the levels of BAT-related molecular markers were decreased in LmnaG609G/G609G mice at 14 weeks of age. The aging characteristics and the aging mechanism of BAT in LmnaG609G/G609G mice can mimic normal BAT aging. Key words: LmnaG609G/G609G mice, BAT, aging, 18F-FDG PET/CT