Format

Send to

Choose Destination
Cell Metab. 2016 Feb 9;23(2):315-23. doi: 10.1016/j.cmet.2015.11.003. Epub 2015 Dec 6.

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

Author information

1
Department of Cancer Biology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA.
2
Department of Oral Medicine, Infection, and Immunity, Harvard School of Dental Medicine, Boston, MA 02115, USA.
3
Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
4
Department of Cancer Biology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA. Electronic address: bruce_spiegelman@dfci.harvard.edu.

Abstract

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.

KEYWORDS:

PTHrP; adipose tissue browning; cachexia; cancer; chronic kidney disease; parathyroid hormone (PTH); skeletal muscle atrophy

PMID:
26669699
PMCID:
PMC4749423
DOI:
10.1016/j.cmet.2015.11.003
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center