Hypothalamic inflammation is reversed by endurance training in anorectic-cachectic rats

Abstract

Aim: We tested the effects of a cancer cachexia-anorexia sydrome upon the balance of anti and pro-inflammatory cytokines in the hypothalamus of sedentary or trained tumour-bearing (Walker-256 carcinosarcoma) rats.

Methods: Animals were randomly assigned to a sedentary control (SC), sedentary tumour-bearing (ST), and sedentary pair-fed (SPF) groups or, exercised control (EC), exercised tumour-bearing (ET) and exercised pair-fed (EPF) groups. Trained rats ran on a treadmill (60%VO2max) for 60 min/d, 5 days/wk, for 8 wks. We evaluated food intake, leptin and cytokine (TNF-α, IL1β) levels in the hypothalamus.

Results: The cumulative food intake and serum leptin concentration were reduced in ST compared to SC. Leptin gene expression in the retroperitoneal adipose tissue (RPAT) was increased in SPF in comparison with SC and ST, and in the mesenteric adipose tissue (MEAT) the same parameter was decreased in ST in relation to SC. Leptin levels in RPAT and MEAT were decreased in ST, when compared with SC. Exercise training was also able to reduce tumour weight when compared to ST group. In the hypothalamus, IL-1β and IL-10 gene expression was higher in ST than in SC and SPF. Cytokine concentration in hypothalamus was higher in ST (TNF-α and IL-1β, p < 0.05), compared with SC and SPF. These pro-inflammatory cytokines concentrations were restored to control values (p < 0.05), when the animals were submitted to endurance training.

Conclusion: Cancer-induced anorexia leads towards a pro-inflammatory state in the hypothalamus, which is prevented by endurance training which induces an anti-inflammatory state, with concomitant decrease of tumour weight.

Figure 1

Hypothalamic cytokine levels and it respective gene expression interleukin 1β (IL-1β), tumour necrose factor alpha (TNF-α), and interleukin 10 (IL-10) in rats. Results are expressed as mean value ± SEM. SC: sedentary control (n = 7), ST: sedentary tumour-bearing (n = 7), SPF: sedentary pair-fed (n = 7), EC: trained control (n = 6), ET: trained tumour-bearing (n = 6), EPF: trained pair-fed (n = 6). *p < 0.01 vs. sedentary control; #p < 0.01 vs. sedentary tumour-bearing; &p < 0.01 vs. trained control; $p < 0.01 vs. trained tumour-bearing.

Figure 2

The effect of exercise training on tumour weight in cancer-induced anorexia rats. Results are expressed as mean value ± SEM.ST: sedentary tumour-bearing (n = 7) and ET: trained tumour-bearing (n = 6). *p < 0.01 vs. sedentary tumour-bearing.