Abstract

Visceral adipose tissue is an immunogenic tissue, which turns detrimental during obesity by activation of proinflammatory macrophages. During aging, chronic inflammation increases proportional to visceral adipose tissue (VAT) mass and associates with escalating morbidity and mortality. Here, we utilize a mouse model to investigate the inflammatory status of visceral adipose tissue in lean aging mice and assess the effects of exercise training interventions. We randomized adult (11 months; n = 21) and old (23 months; n = 27) mice to resistance training (RT) or endurance training (ET), or to a sedentary control group (S). Strikingly, we observed an anti-inflammatory phenotype in the old mice, consisting of higher accumulation of M2 macrophages and IL-10 expression, compared to the adult mice. In concordance, old mice also had less VAT mass and smaller adipocytes compared to adult mice. In both age groups, exercise training enhanced the anti-inflammatory phenotype and increased PGC1-α mRNA expression. Intriguingly, the brown adipose tissue marker UCP1 was modestly higher in old mice, while remained unchanged by the intervention. In conclusion, in the absence of obesity, visceral adipose tissue possesses a pronounced anti-inflammatory phenotype during aging which is further enhanced by exercise.

Highlights

  • Adipose tissue is host to various immune cells and it is well established that during obesity, the amount of inflammatory macrophages increase in adipose tissue[1,2]

  • The endurance training (ET) groups ran for longer distance compared to resistance training (RT) and a trend were seen for ET mice to have longer training time and velocity compared to RT (p = 0.06 and 0.09 respectively)

  • The differences in visceral adipose tissue phenotype between old and adult mice seemed more pronounced in old mice following endurance exercise training, possibly suggesting higher lipolytic response in the visceral adipose tissue of the old mice compared to the adult

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Summary

Methods

Afterwards samples were allowed to cool to room temperature and washed in TBS From this point, 2 protocols were used to stain for either (1) perilipin or (2) CD206. The following day samples were washed in TBS and incubated with the secondary antibody (Alexa Fluor goat anti-rabbit 568, A-11036, ThermoFisher, 1:500) for 60 minutes 1% BSA in TBS. Samples were subjected to blocking using 5% goat serum, 2% BSA in TBS for 1 hour and incubated overnight at 4 °C with the primary antibody (rabbit anti-CD206, ab64693) at a 1:16000 dilution in blocking buffer. The following day, all sections were incubated with the secondary antibody (ImmPRESS Reagent anti-rabbit, vector MP-7401) for 30 minutes. This fraction (%) was used for subsequent statistical analysis. To obtain Gaussian distributed values, visceral fat mass, adipocyte size, CD206 area fraction and all mRNA analysis were log transformed. All log transformed data are given as geometric mean with back-transformed SE seen in corresponding figures or 95% CI (see Table 1). mRNA results are shown as relative change, compared to the AS group

Results
Discussion
B CD206 area staining
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