Wang explains that the researchers “were curious whether adipogenesis takes place as we reach middle age,” as “starting from mid-age and continuing into early aging, adults often experience a significant increase in visceral fat tissue [while] the adipogenesis rate in young adults is very low.” To track adipogenesis, the authors used AdipoChaser mice, which express a doxycycline-inducible GFP reporter in mature adipocytes. In this study, 3-month-old AdipoChaser male mice were treated with doxycycline, which effectively tagged all mature adipocytes present at that age with GFP, but not any adipocytes generated after that point. After these mice reached 6, 9 or 12 months of age, the authors looked at the number of GFP− cells in the gonadal WAT (a typical visceral WAT) that expressed the adipocyte marker perilipin (which would represent mature adipocytes that had emerged after doxycycline treatment). The authors observed a significant increase in the number of new, mature adipocytes in mice aged 9–12 months old as compared with 3-month-old animals, which suggests increased adipogenesis in these older animals. The authors also found that gonadal WAT APCs in 12-month-old mice were more proliferative and adipogenic once transplanted into younger animals, as compared with APCs taken from 2.5-month-old mice.
The next step, explained Yang, was “to further understand the cellular and molecular mechanisms driving adipogenesis during mid-age,” by using “single-cell RNA sequencing [scRNA-seq] to examine the APC populations and trajectories” in gonadal WAT from 2.5-month-old or 12-month-old mice. The authors identified 5 clusters of cells across WAT samples, including a population of APCs that were enriched with age (termed CP-As) in 12-month-old mice, which were marked by high Lifr expression. CP-A-like cells were also identified in human peripancreatic WAT (which is also a typical visceral WAT) on the basis of scRNA-seq profiling of samples from 5 individuals aged 21–57 years old. The CP-As found in 12-month-old mice were more proliferative and adipogenic than APCs enriched in younger animals. Wang concluded that “the adipogenic potential of APCs is unlocked with age, accompanied by the generation of a new committed preadipocyte population, the CP-As, that has high adipogenic activity.”
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