Increase in skeletal muscle protein content by the beta-2 selective adrenergic agonist clenbuterol exacerbates hypoalbuminemia in rats fed a low-protein diet.

Abstract

This investigation examined how the nutritional status of rats fed a low-protein diet was affected when the animals were treated with the beta-2 selective agonist clenbuterol (CL). Males (4 weeks old) from an inbred, specific-pathogen-free strain of hooded rats maintained at the Dunn Nutritional Laboratory were used in the experiments (N = 6 rats per group). CL treatment (Ventipulmin, Boehringer-Ingelheim Ltd., 3.2 mg/kg diet for 2 weeks) caused an exacerbation of the symptoms associated with protein deficiency in rats. Plasma albumin concentrations, already low in rats fed a low-protein diet (group A), were further reduced in CL rats (A = 25.05 +/- 0.31 vs CL = 23.64 +/- 0.30 g/l, P < 0.05). Total liver protein decreased below the level seen in either pair-fed animals (group P) or animals with free access to the low-protein diet (A = 736.56 +/- 26 vs CL = 535.41 +/- 54 mg, P < 0.05), whereas gastrocnemius muscle protein was higher than the values normally described for control (C) animals (C = 210.88 +/- 3.2 vs CL = 227.14 +/- 1.7 mg/g, P < 0.05). Clenbuterol-treated rats also showed a reduction in growth when compared to P rats (P = 3.2 +/- 1.1 vs CL = -10.2 +/- 1.9 g, P < 0.05). This was associated with a marked decrease in fat stores (P = 5.35 +/- 0.81 vs CL = 2.02 +/- 0.16 g, P < 0.05). Brown adipose tissue (BAT) cytochrome oxidase activity, although slightly lower than in P rats (P = 469.96 +/- 16.20 vs CL = 414.48 +/- 11.32 U/BAT x kg body weight, P < 0.05), was still much higher than in control rats (C = 159.55 +/- 11.54 vs CL = 414.48 +/- 11.32 U/BAT x kg body weight, P < 0.05). The present findings support the hypothesis that an increased muscle protein content due to clenbuterol stimulation worsened amino acid availability to the liver and further reduced albumin synthesis causing exacerbation of hypoalbuminemia in rats fed a low-protein diet.