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

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.

Low-grade chronic inflammation is attenuated by exercise training in obese adults through down-regulation of ASC gene in peripheral blood: a pilot study

“…Therefore, we could expect from our ndings that the exercise program had a role in the decrease of NLRP3 in ammasome activation through ASC down-regulation, MCP-1, and MIP-1β; thus, improving the anti-in ammatory pro le through the IL-10 cytokine. Moreover, visceral adipose tissue surrounding the internal organs has in ammatory activity since it is associated with a greater number of pro-in ammatory cells in the tissue [31]. Therefore, the decreased levels of MCP-1, MIP-1β and IL-8 cytokines in our study also may be in part due to the abdominal fat loss, since these results showed a positive correlation between them (p<0.05).…”

Is Exercise a Match for Cold Exposure? Common Molecular Framework for Adipose Tissue Browning

“…Within BAT, treadmill training for 1 week was shown to increase PGC-1α [81,109], while voluntary wheel running for 11 days to 3 weeks and prolonged treadmill training (8 weeks) yielded no changes or decreases in PGC-1α [21,22,95,99,101]. Within WAT, PGC-1α seems to be more potently activated by exercise in both humans [116,117] and rodents [8,22,62,[99][100][101][111][112][113][114][115]. Swimming both acutely (2 h) and chronically (8 weeks) increased PGC-1α in subcutaneous WAT and epididymal WAT, with inconsistent increases or no change in inguinal WAT and visceral WAT [8,62,101,111,181].…”

“…In rodents, acute [8,62] and chronic exercise from 1-3 weeks [99][100][101]111] increased PGC-1α mRNA. Likewise, 8-10 weeks of protocols involving running (treadmill, voluntary wheel running, endurance training) and resistance training [22,[112][113][114][115] increased PGC-1α. In humans, PGC-1α mRNA increased in subcutaneous and omental WAT in response to 4-6 weeks of aerobic training [116,117].…”

“…Though FGF21 is mainly released by hepatocytes into circulation [119], its expression can be induced in skeletal muscle in response to acute exercise [120,121]. A co-receptor of FGF21, ßKlotho, is a singletransmembrane protein essential for FGF21 activity, which is abun- R [180] ↑mRNA in sWAT swim training (30d) R [100] ↑mRNA, protein in iWAT treadmill training (5 wk) R [56], [98] ↑mRNA in sWAT resistance training (8 wk) R [199] ↑mRNA in sWAT aerobic training (8 wk) R [200] ↑mRNA in sWAT treadmill (8 wk) R [22], [95], [185] mRNA in vWAT treadmill (8 wk) R [22], [185] ↑mRNA in eWAT treadmill training (8 wk) R [21] ↑protein in eWAT treadmill training (8 wk) R [112] ↑mRNA in iWAT treadmill training (8 wk) R [113] ↑protein in iWAT voluntary wheel running (10 wk) R [114] protein in eWAT voluntary wheel running (10 wk) R [114] mRNA in eWAT resistance, endurance training (10 wk) R [115] mRNA in sWAT endurance, interval training (10 wk) dantly found in adipose tissue, but not skeletal muscle [122,123]. This enables FGF21 to have unique actions on adipose tissue and skeletal muscle upon release [124].…”

“…Irisin is secreted from myocytes in response to cold exposure, although its release parallels shivering intensity, suggesting that it may evolve from shivering-induced muscle contractions [153]. This protein in sWAT voluntary wheel running (3 wk) R [183] mRNA in iWAT treadmill training (5 wk) R [56] mRNA in iWAT swimming (8 wk) R [181] ↑mRNA in sWAT treadmill training (8 wk) R [22] mRNA in sWAT treadmill training (8 wk) R [95] mRNA in vWAT treadmill training (8 wk) R [22], [162] mRNA in eWAT treadmill training (8 wk) R [21] ↑protein in eWAT treadmill training (8 wk) R [112] ↑mRNA in iWAT treadmill training (8 wk) R [113] ↑protein in iWAT, eWAT voluntary wheel running (10 wk) R [114] ↑mRNA in eWAT resistance, endurance training (10 wk) R [115] UCP1: Uncoupling Protein-1; PGC-1α: peroxisome proliferator-activated receptor C co-activator-1α; Sp: Species; R: rodents; H: humans; ~: No change; iWAT: inguinal white adipose tissue; sWAT: subcutaneous white adipose tissue; eWAT: epididymal white adipose tissue; vWAT: visceral adipose tissue; rpWAT: retroperitoneal white adipose tissue; oWAT: omental white adipose tissue; CWI: cold water immersion. is further corroborated by the absence of increases in circulating irisin levels in response to mild cold exposure at 19 °C, a temperature insufficient to induce shivering [133,154]…”