Targeting both sides of the GDF15-GFRAL-RET receptor complex: A new approach to achieve body weight homeostasis

Fei Li; Xiongzhong Ruan; Le Min

doi:10.1016/j.gendis.2017.11.004

Targeting both sides of the GDF15-GFRAL-RET receptor complex: A new approach to achieve body weight homeostasis

Genes Dis. 2017 Nov 21;4(4):183-184. doi: 10.1016/j.gendis.2017.11.004. eCollection 2017 Dec.

Authors

Fei Li¹, Xiongzhong Ruan², Le Min³

Affiliations

¹ The Editorial Office of Genes & Diseases, Chongqing Medical University, Chongqing, China.
² John Moorhead Research Laboratory, Centre for Nephrology, University College London, London, UK.
³ Division of Endocrinology, Diabetes, and Hypertension, Brigham and Women's Hospital, Boston, MA, United States.

Abstract

Obesity is a chronic, complex disease, which is associated with several comorbidities, including diabetes mellitus, hypertension, and cardiovascular diseases. It is estimated that the prevalence of obesity among both adults and children nearly tripled between 1975 and 2016, highlighting a huge unmet treatment need. However, the currently available anti-obesity drugs have serious side effects, which limit their long-term use. The finding that the newly-identified brain GDF15-GFRAL-RET receptor signaling complex is involved in stress/disease-induced anorexia will certainly impact our knowledge of body weight homeostasis under healthy and disease conditions. Based on this breakthrough, a new class of GFRAL/RET-based drugs is highly anticipated for the treatment of obesity, as well as cancer-induced cachexia.

Keywords: Anorexia; Brain; GDF15; GFRAL; MIC-1; Obesity; RET.