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Parathyroid hormone stimulates adipose tissue browning: a pathway to muscle wasting

Thomas, Sandhya S.; Mitch, William E.

Current Opinion in Clinical Nutrition & Metabolic Care: May 2017 - Volume 20 - Issue 3 - p 153–157
doi: 10.1097/MCO.0000000000000357
TRANSLATIONAL RESEARCH IN WASTING DISEASES: Edited by Claude Pichard and Didier Attaix

Purpose of review: Studying organ-to-organ communications (i.e. crosstalk) uncovers mechanisms regulating metabolism in several tissues. What is missing is identification of mediators of different catabolic conditions contributing to losses of adipose and muscle tissues. Identifying mediators involved in organ-to-organ crosstalk could lead to innovative therapeutic strategies because several disorders such as chronic kidney disease (CKD), cancer cachexia, and other catabolic conditions share signals of worsening metabolism and increased risk of mortality.

Recent findings: A recent breakthrough published in Cell Metabolism leads to the conclusion that parathyroid hormone (PTH) and parathyroid hormone-related peptide (PTHrP) cause ‘browning’ of white adipose tissue plus energy production via activation of uncoupling protein-1. Browning was associated with muscle wasting in mouse models of cancer and CKD. The pathway to browning includes PTH/PTHrP activation of protein kinase A (PKA) and lost muscle mass via the ubiquitin proteasome proteolytic system (UPS).

Summary: The results suggest that crosstalk between muscle and fat contributes in a major way to tissue catabolism. The pathway initiated by PTH or PTHrP is novel and it suggests potential interrelationships that control metabolism in other catabolic conditions. Identifying how the parathyroid hormone–PKA–UPS axis relates to obesity, type 2 diabetes, and other insulin-resistant conditions remains unclear.

aMichael E. Debakey Veterans Affair Medical Center

bDivision of Nephrology, Selzman Institute for Kidney Health, Baylor College of Medicine, One Baylor Plaza, Houston, Texas, USA

Correspondence to Sandhya S. Thomas, MD, One Baylor Plaza, BCM 395, Houston, TX 77030, USA. Tel: +1 713 798 2402; fax: +1 713 798 5010; e-mail: ssthomas@bcm.edu

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