Sympathetic activation of brown-adipose-tissue thermogenesis in cachexia

Abstract

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.

PTH/PTHrP Receptor Mediates Cachexia in Models of Kidney Failure and Cancer

“…Both brown and beige fat cells are also found in humans and play a role in energy homeostasis (Cypess et al, 2013; Virtanen et al, 2009). Several studies have described activation of brown fat in rodent models of cancer cachexia; anecdotal reports also show activated brown fat in at least some cachectic patients (Bianchi et al, 1989; Bing et al, 2000; Brooks et al, 1981; Roe et al, 1996; Shellock et al, 1986; Tsoli et al, 2012). Recently, “browning” of the white fat depots has been shown to drive wasting in rodent models of cancer cachexia (Kir et al, 2014; Petruzzelli et al, 2014; Tsoli et al, 2012).…”

Molecular and neuroendocrine mechanisms of cancer cachexia

“…2). Interestingly, cancer-associated cachexia increases energy expenditure, an effect mainly mediated by the BAT and coordinated by the hypothalamus (Brooks et al 1981, Bianchi et al 1989, Tsoli et al 2012, Kir et al 2014. This organ senses the increased levels of TNF, the tyrotropin-releasing hormone, and the corticotropin-releasing hormone to promote heat production via a B3-adrenergic neuronal circuit (Arruda et al 2011).…”

Molekulare und metabolische Komponenten der Tumorkachexie

“…B. in interskapularen Depots der Maus oder von Neugeborenen [13]. Interessanterweise konnte bereits vor fast 30 Jahren eine Aktivierung der Thermogenese im braunen Fettgewebe bei der Tumorkachexie nachgewiesen [9] und eine Expansion des braunen Fettgewebes bei tumorkachektischen Patienten dokumentiert werden [22]. Tat …”