A Switch from White to Brown Fat Increases Energy Expenditure in Cancer-Associated Cachexia

Michele Petruzzelli, Martina Schweiger, Renate Schreiber, Ramon Campos-Olivas, Maria Tsoli, John Allen, Michael Swarbrick, Stefan Rose-John, Mercedes Rincon, Graham Robertson, Rudolf Zechner, Erwin F. Wagner

Highlights

• WAT browning contributes to high energy expenditure in cancer-associated cachexia
• Systemic inflammation and IL-6 induce and sustain WAT browning in cachexia
• Inhibition of WAT browning ameliorates the severity of cachexia
• Cancer cachexia patients stain positive for UCP1 protein in WAT

Cell Metabolism Available online 17 July 2014. In Press, Corrected Proof — Note to users
DOI: http://dx.doi.org/10.1016/j.cmet.2014.06.011

Fuente: Echa un vistazo al Tweet de @elmundosalud

Summary: 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.

Cell Metabolism Available online 17 July 2014. In Press, Corrected Proof — Note to users
DOI: http://dx.doi.org/10.1016/j.cmet.2014.06.011

Fuente: Echa un vistazo al Tweet de @elmundosalud

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