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

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-alpha, IL1 beta) 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-1 beta and IL-10 gene expression was higher in ST than in SC and SPF. Cytokine concentration in hypothalamus was higher in ST (TNF-alpha and IL-1 beta, 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.