Format

Send to

Choose Destination
See comment in PubMed Commons below
Cell Metab. 2014 Sep 2;20(3):433-47. doi: 10.1016/j.cmet.2014.06.011. Epub 2014 Jul 17.

A switch from white to brown fat increases energy expenditure in cancer-associated cachexia.

Author information

1
BBVA Foundation-CNIO Cancer Cell Biology Programme, Spanish National Cancer Research Centre (CNIO), C/ Melchor Fernández Almagro 3, 28029 Madrid, Spain.
2
Institute of Molecular Biosciences, University of Graz, Humboldtstrasse 50, 8010 Graz, Austria.
3
Spectroscopy and Nuclear Magnetic Resonance Unit, Spanish National Cancer Research Centre (CNIO), C/ Melchor Fernández Almagro 3, 28029 Madrid, Spain.
4
Children's Cancer Institute Australia for Medical Research, UNSW Lowy Cancer Research Centre Building, C25 Kensington Campus UNSW, Sydney, NSW 2052, Australia.
5
Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, NSW 2010, Australia.
6
Institute of Biochemistry, Christian-Albrechts University, Olshausenstr. 40, 24118 Kiel, Germany.
7
Division of Immunobiology, Department of Medicine, University of Vermont, 89 Beaumont Avenue / D305 Given Building, Burlington, VT 05405, USA.
8
BBVA Foundation-CNIO Cancer Cell Biology Programme, Spanish National Cancer Research Centre (CNIO), C/ Melchor Fernández Almagro 3, 28029 Madrid, Spain. Electronic address: ewagner@cnio.es.

Abstract

Cancer-associated cachexia (CAC) is a wasting syndrome characterized by systemic inflammation, body weight loss, atrophy of white adipose tissue (WAT) and skeletal muscle. Limited therapeutic options are available and the underlying mechanisms are poorly defined. Here we show that a phenotypic switch from WAT to brown fat, a phenomenon termed WAT browning, takes place in the initial stages of CAC, before skeletal muscle atrophy. WAT browning is associated with increased expression of uncoupling protein 1 (UCP1), which uncouples mitochondrial respiration toward thermogenesis instead of ATP synthesis, leading to increased lipid mobilization and energy expenditure in cachectic mice. Chronic inflammation and the cytokine interleukin-6 increase UCP1 expression in WAT, and treatments that reduce inflammation or β-adrenergic blockade reduce WAT browning and ameliorate the severity of cachexia. Importantly, UCP1 staining is observed in WAT from CAC patients. Thus, inhibition of WAT browning represents a promising approach to ameliorate cachexia in cancer patients.

PMID:
25043816
DOI:
10.1016/j.cmet.2014.06.011
[Indexed for MEDLINE]
Free full text
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science
    Loading ...
    Support Center