PTH/PTHrP Receptor Mediates Cachexia in Models of Kidney Failure and Cancer.

Published

Journal Article

Cachexia is a wasting syndrome associated with elevated basal energy expenditure and loss of adipose and muscle tissues. It accompanies many chronic diseases including renal failure and cancer and is an important risk factor for mortality. Our recent work demonstrated that tumor-derived PTHrP drives adipose tissue browning and cachexia. Here, we show that PTH is involved in stimulating a thermogenic gene program in 5/6 nephrectomized mice that suffer from cachexia. Fat-specific knockout of PTHR blocked adipose browning and wasting. Surprisingly, loss of PTHR in fat tissue also preserved muscle mass and improved muscle strength. Similarly, PTHR knockout mice were resistant to cachexia driven by tumors. Our results demonstrate that PTHrP and PTH mediate wasting through a common mechanism involving PTHR, and there exists an unexpected crosstalk mechanism between wasting of fat tissue and skeletal muscle. Targeting the PTH/PTHrP pathway may have therapeutic uses in humans with cachexia.

Full Text

Duke Authors

Cited Authors

  • Kir, S; Komaba, H; Garcia, AP; Economopoulos, KP; Liu, W; Lanske, B; Hodin, RA; Spiegelman, BM

Published Date

  • February 2016

Published In

Volume / Issue

  • 23 / 2

Start / End Page

  • 315 - 323

PubMed ID

  • 26669699

Pubmed Central ID

  • 26669699

Electronic International Standard Serial Number (EISSN)

  • 1932-7420

International Standard Serial Number (ISSN)

  • 1550-4131

Digital Object Identifier (DOI)

  • 10.1016/j.cmet.2015.11.003

Language

  • eng