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Kir et al. A common mechanism for tumor-induced cachexia and CKD
DOI:10.1038/bonekey.2016.37
Kir et al. used nephrectomized mice, an established model of kidney failure, to study the role of parathyroid hormone (PTH) in cachexia, the wasting syndrome often seen in patients with chronic kidney disease (CKD) and advanced cancers.
The mice had elevated levels of PTH and exhibited a cachexia phenotype with a reduction in body weight, loss of muscle mass and an increase in brown fat tissue, which increased energy expenditure. The authors concluded that the hypermetabolism observed in these animals is probably due to a PTH-driven upregulation of thermogenesis in fat deposits. They further suggest that parathyroid hormone-related protein (PTHrP) derived from tumors has the same effects.
When the PTHR gene was knocked out in fat tissue specifically in this model, both muscle wasting and adipose tissue browning were prevented. In fact, muscle mass and muscle strength actually improved. The authors conclude that muscle wasting in cachexia and in CKD may have a common origin.
Editor’s comment: Ogata et al. originally proposed that tumor-derived PTHrP is responsible for cachexia. This study extends our understanding of the role of PTH/PTHrP receptor signal not only in tumor-induced cachexia but also in renal failure with elevated PTH. In order to apply these observations to CKD patients, it will be necessary to study the effects of blocking the PTH/PTHrP receptor signal specifically in adipocytes.
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