Synergistic effect of carnosine on browning of adipose tissue in exercised obese rats; a focus on circulating irisin levels

The recent appreciation of the energy burning capacity of brown adipose tissue turns it to an attractive target for anti-obesity therapy. We sought to evaluate the effect of L-carnosine on browning of white adipose tissue in exercised obese rats. Sixty adult male Wistar albino rats, 7-8 week-old weighing 130-150g, were allocated into six groups; with 10 rats in each, for an experimentation period of 12 weeks: (i) normal control rats fed a standard fat diet (SFD/control), (ii) normal control rats fed a standard diet and injected with L-carnosine (250 mg/kg, i.p,) for 6 weeks (SFD/CAR), (iii) high-fat diet (HFD)-induced obese rats for 12 weeks, (iv) HFD rats subjected to exercise training (HFD/EXE) for 6 weeks, (v) HFD rats injected with L-carnosine (250 mg/kg,i.p.) for 6 weeks (HFD/CAR) and, (vi) HFD rats subjected to exercise training and L-carnosine (HFD/EXE/CAR). At the end of the 12-week-experiment, the body weights and the serum levels of lipid profile, oxidative stress, and inflammatory markers as well as circulating myokines were investigated. Gastrocnemius muscles and inguinal adipose tissues were excised for the measurement of gene expression of muscle irisin, adipose tissue uncoupling protein1 (UCP1), CD137 and the protein level of p38MAPK. In addition, histopathological examination for the studied groups was performed. Both exercise training for 6 weeks and carnosine treatment significantly decreased body weight gain, ameliorated obesity-induced dyslipidemia, reduced the thiobarbituric acid reactive species (TBARS) and TNF-, while increased total antioxidant capacity and IL-10. Furthermore, increases in serum irisin levels and the expression of adipose uncoupling protein-1 (UCP-1), adipose CD137, p38 MAPK, and muscular fibronectin type III domain-containing protein 5(FNDC5), the precursor of irisin gene expression, were correlated with these carnosine- and exercise-induced physiological improvements. The highest improvement was evident in the combined exercise and carnosine group which indicates that their beneficial effects in obese animals were synergistic. These findings suggest that L-carnosine may induce browning of adipose tissue through irisin stimulation, a phenomenon that could be related to its antioxidant, anti-inflammatory, and anti-obesity effects.