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Activation of thermogenesis in brown adipose tissue and dysregulated lipid metabolism associated with cancer cachexia in mice

Tsoli, Maria, Moore, Melissa, Burg, Dominic, Painter, Aarran, Taylor, Ryland, Lockie, Sarah H., Turner, Nigel, Warren, Aleaandra, Cooney, Greg, Oldfield, Brian, Clarke, Stephen and Robertson, Graham (2012) Activation of thermogenesis in brown adipose tissue and dysregulated lipid metabolism associated with cancer cachexia in mice Cancer Research, 72, (17), pp. 4372-4382. (doi:10.1158/0008-5472.CAN-11-3536). (PMID:22719069).

Record type: Article

Abstract

Cancer cachexia/anorexia is a complex syndrome that involves profound metabolic imbalances and is directly implicated as a cause of death in at least 20% to 30% of all cancers. Brown adipose tissue (BAT) plays a key role in thermogenesis and energy balance and potentially contributes to the physiologic perturbations associated with cachexia. In this study, we investigated the impact of cachexia-inducing colorectal tumor on BAT in mice. We found that brown adipocytes were smaller and exhibited profound delipidation in cachectic tumor–bearing mice. Diurnal expression profiling of key regulators of lipid accumulation and fatty acid ?-oxidation and their corresponding target genes revealed dramatic molecular changes indicative of active BAT. Increased Ucp1, Pbe, and Cpt1? expression at specific points coincided with higher BAT temperatures during the dark cycle, suggestive of a temporal stimulation of thermogenesis in cachexia. These changes persisted when cachectic mice were acclimatized to 28°C confirming inappropriate stimulation of BAT despite thermoneutrality. Evidence of inflammatory signaling also was observed in the BAT as an energetically wasteful and maladaptive response to anorexia during the development of cachexia.

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Accepted/In Press date: 19 June 2012
Published date: 1 September 2012
Organisations: Molecular and Cellular

Identifiers

Local EPrints ID: 343044
URI: http://eprints.soton.ac.uk/id/eprint/343044
ISSN: 0008-5472
PURE UUID: edf2082e-22b4-4f70-ac84-c7a6feec7517

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Date deposited: 21 Sep 2012 10:49
Last modified: 18 Jul 2017 05:25

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Contributors

Author: Maria Tsoli
Author: Melissa Moore
Author: Dominic Burg
Author: Aarran Painter
Author: Ryland Taylor
Author: Sarah H. Lockie
Author: Nigel Turner
Author: Aleaandra Warren
Author: Greg Cooney
Author: Brian Oldfield
Author: Stephen Clarke
Author: Graham Robertson

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