guanosine-diphosphate and Cachexia

Despite anorexia, cancer development is frequently accompanied by an increase of energy expenditure. Considering the pivotal role played by brown adipose tissue (BAT) in the energy metabolism of small mammals, we investigated the functional and compositional modification in BAT of anorexic tumor-bearing (Yoshida sarcoma) and pair-fed control rats. BAT thermogenic activity (assessed by maximal mitochondrial GDP binding) was 1.8-fold greater in tumor-bearing rats than in controls, while the thermogenic capacity (assessed by measurement of uncoupling protein) was unchanged. This suggests that tumor bearing had induced an unmasking of uncoupling protein sites. BAT hypertrophy and hyperplasia, characteristic of full-fledged BAT activation, did not occur. The mitochondrial oxidative capacity of BAT (assessed by cytochrome c oxidase activity) was 1.6-fold lower in tumor-bearing than in control rats. The main compositional modification observed in BAT of tumor-bearing rats was an increase in the saturation of cardiolipin fatty acids. These results suggest that the BAT stimulation induced by tumor bearing after 10 days is almost exclusively functional and that the tissue development is limited, probably by anorexia. However, a suppressive effect of anorexia inhibition by tumor bearing cannot be excluded.

Topics: Adipose Tissue, Brown; Animals; Anorexia; Body Temperature Regulation; Body Weight; Cachexia; Cardiolipins; Eating; Electron Transport Complex IV; Fatty Acids; Guanosine Diphosphate; In Vitro Techniques; Male; Mitochondria; Rats; Rats, Wistar; Sarcoma, Yoshida; Uncoupling Agents

Tumour-bearing mice spontaneously lose weight 8-9 weeks after implantation of a human hypernephroma, in spite of a normal food intake. Resting oxygen consumption was up to 40% higher in these animals than in sham-operated controls, but was significantly reduced by beta-adrenergic blockade with propranolol in the former group. The injection of noradrenaline caused a marked stimulation of the metabolic rate in all the animals, but the greatest response was seen in the cachectic mice. The brown-adipose-tissue mass was similar for both groups, but guanosine diphosphate binding to brown-adipose-tissue mitochondria (an index of thermogenic capacity) was significantly increased in tumor-bearing mice, and the injection of noradrenaline 1 h prior to sacrifice caused the greatest stimulation of binding in the cachectic group. These data suggest that the rapid weight loss of tumor-bearing animals may be due to a high metabolic rate which results from sympathetic stimulation of brown-adipose-tissue metabolism. The relevance of these results to cancer-induced cachexia in man is discussed.

Topics: Adipose Tissue, Brown; Animals; Cachexia; Female; Guanine Nucleotides; Guanosine Diphosphate; Mice; Mitochondria; Neoplasms, Experimental; Norepinephrine; Oxygen Consumption; Propranolol; Sympathetic Nervous System