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Semin Cell Dev Biol. 2016 Jun;54:68-81. doi: 10.1016/j.semcdb.2015.10.039. Epub 2015 Oct 31.

Lipolytic and thermogenic depletion of adipose tissue in cancer cachexia.

Author information

1
Children's Cancer Institute, Lowy Cancer Research Centre, University of New South Wales, Randwick, NSW 2031, Australia.
2
Centre for Diabetes, Obesity and Endocrinology, The Westmead Institute for Medical Research, The University of Sydney, NSW, Australia.
3
School of Molecular Biosciences, University of Sydney, NSW 2006, Australia. Electronic address: graham.robertson@sydney.edu.au.

Abstract

Although muscle wasting is the obvious manifestation of cancer cachexia that impacts on patient quality of life, the loss of lipid reserves and metabolic imbalance in adipose tissue also contribute to the devastating impact of cachexia. Depletion of fat depots in cancer patients is more pronounced than loss of muscle and often precedes, or even occurs in the absence of, reduced lean body mass. Rapid mobilisation of triglycerides stored within adipocytes to supply the body with fatty acids in periods of high-energy demand is normally mediated through a well-defined process of lipolysis involving the lipases ATGL, HSL and MGL. Studies into how these lipases contribute to fat loss in cancer cachexia have revealed the prominent role for ATGL in initiating lipolysis during adipose tissue atrophy, together with links between tumour-derived factors and the signalling pathways that control lipid flux within fat cells. The recent findings of increased thermogenesis in brown fat during cancer cachexia indicate that metabolically active adipose tissue contributes to the imbalance in energy homeostasis involved in catabolic wasting. Such energetically futile use of fatty acids liberated from adipose tissue to generate heat represents a maladaptive response in conjunction with anorexia experienced by cancer patients. As IL-6 release by tumours provokes lipolysis and activates the thermogenic programme in brown fat, this review explores the overlap in dysregulated metabolic processes due to inflammatory mediators in cancer cachexia and other disease states characterised by elevated cytokines such as obesity and diabetes.

KEYWORDS:

Adipose tissue; Brown fat; Cancer cachexia; IL-6; Lipolysis; Thermogenesis

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