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. 2019 Aug 19;9(1):12069.
doi: 10.1038/s41598-019-48587-2.

An anti-inflammatory phenotype in visceral adipose tissue of old lean mice, augmented by exercise

A K Ziegler  1   2 , A Damgaard  3 , A L Mackey  3   4 , P Schjerling  3 , P Magnusson  3   5 , A T Olesen  3 , M Kjaer  3   4 , C Scheele  6   7
Affiliations

An anti-inflammatory phenotype in visceral adipose tissue of old lean mice, augmented by exercise

A K Ziegler et al. Sci Rep. .

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.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1
Figure 1
Characteristics of visceral adipose tissue in adult and old mice following exercise training interventions. We characterized the epididymal adipose depot of adult and old mice that were sedentary (S) or had performed either resistance training (RT) or endurance training (ET). (A) Representative pictures of perilipin-stained epididymal adipose of adult (top) and old (bottom) mice divided by intervention, 20x objective. (B) Average adipocyte area (µm2) measured from 200 adipocytes, based on the perilipin staining. (C) Total weight of epididymal adipose depot (mg). (B,C) Geometric mean ± SE. (B,C) Y-axis given as log2. *Significantly different from S. Scalebar: 100 µm. Adult S (AS) n = 7, Adult RT (ART) n = 7, Adult ET (AET) n = 7, Old S (OS) n = 10 Old RT (ORT) n = 6; Old ET (OET) n = 6.
Figure 2
Figure 2
Immunogenic phenotype of visceral adipose tissue in adult and old mice following exercise training interventions. Epididymal adipose from the groups depicted in Fig. 1 were characterized for anti- and pro-inflammatory markers (A) Representative images showing CD206 enzymatic staining (brown) using bright field microscopy, 20x objective. (B) Quantification of the percentage of total area staining positive for CD206 from 4 snapshots from each mouse. (C) Relative gene expression levels of the anti-inflammatory markers, IL-10 and adiponectin. (D) Relative gene expression levels of the pro-inflammatory markers, TNF-α and IL-6. Y-axis for all figures given as log2. Data given as geometric mean ± SE. *Significantly different from S. AS n = 7, AET n = 7, ART n = 7, OS n = 10, OET n = 6, ORT n = 6. Scalebar: 100 µm.
Figure 3
Figure 3
Markers of fibrosis. (A) Gene-expression of fibrosis marker TGF-β1 (relative change) in epididymal adipose tissue compared to AS (AS, n = 7, ART, n = 7, AET, n = 7, OS, n = 10, ORT, n = 6, OET, n = 6). Data given as geometric mean ± SE. Y-axis given as log2. (B) Picrosirius red staining of VAT in old sedentary mouse revealed no apparent fibrosis in between adipocytes. Brightfield, 20x objective. Scalebar 100 µm.
Figure 4
Figure 4
Oxidative markers. Relative gene expression levels in the epididymal adipose tissue from the groups depicted in Fig. 1 were assessed using qPCR. (A) Relative gene expression levels of PPARGC-1α, a marker for oxidative capacity (AS, n = 7, ART, n = 7, AET, n = 7, OS, n = 10, ORT, n = 6, OET, n = 6). (B) Relative gene expression levels of UCP-1, a marker for browning (AS, n = 7, ART, n = 7, AET, n = 7, OS, n = 10, ORT, n = 6, OET, n = 5). Data given as geometric mean ± SE. *Significantly different from S. $Significantly different from RT. Y-axis given as log2 for both figures.
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