TY - JOUR
AU - Breit, Samuel
AB - Background Elevated circulating levels of the divergent transforming growth factor-beta (TGFb) family cytokine, growth differentiation factor 15 (GDF15), acting through its CNS receptor, glial-derived neurotrophic factor receptor alpha-like (GFRAL), can cause anorexia and weight loss leading to anorexia/cachexia syndrome of cancer and other diseases. Pre- clinical studies suggest that administration of drugs based on recombinant GDF15 might be used to treat severe obesity. However, the role of the GDF15–GFRAL pathway in the physiological regulation of body weight and metabolism is unclear. The critical site of action of GFRAL in the CNS has also not been proven beyond doubt. To investigate these two aspects, we have inhibited the actions of GDF15 in mice started on high-fat diet (HFD). Methods The actions of GDF15 were inhibited using two methods: (1) Groups of 8 mice under HFD had their endogenous GDF15 neutralised by monoclonal antibody treatment, (2) Groups of 15 mice received AAV-shRNA to knockdown GFRAL at its hypothesised major sites of action, the hindbrain area postrema (AP) and the nucleus of the solitary tract (NTS). Metabolic measurements were determined during both experiments. Conclusions Treating mice with monoclonal antibody to GDF15 shortly after commencing HFD results in more rapid gain of body 
TI - GDF15 mediates adiposity resistance through actions on GFRAL neurons in the hindbrain AP/NTS
JF - International Journal of Obesity
DO - 10.1038/s41366-019-0365-5
DA - 2019-05-31
UR - https://www.deepdyve.com/lp/springer-journals/gdf15-mediates-adiposity-resistance-through-actions-on-gfral-neurons-LKbELt3nN8
SP - 2370
EP - 2380
VL - 43
IS - 12
DP - DeepDyve
ER -