Sympathetic activation of brown-adipose-tissue thermogenesis in cachexia.
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.
D002001:Adipose Tissue, Brown / Q000378:metabolism*; D000818:Animals; D002100:Cachexia / Q000503:physiopathology*; D005260:Female; D006150:Guanine Nucleotides / Q000378:metabolism*; D006153:Guanosine Diphosphate / Q000378:metabolism*; D051379:Mice; D008928:Mitochondria / Q000378:metabolism; D009374:Neoplasms, Experimental / Q000503:physiopathology*; D009638:Norepinephrine / Q000494:pharmacology; D010101:Oxygen Consumption / Q000187:drug effects; D011433:Propranolol / Q000494:pharmacology; D013564:Sympathetic Nervous System / Q000503:physiopathology*
D006150:Guanine Nucleotides; D006153:Guanosine Diphosphate; D011433:Propranolol; D009638:Norepinephrine