GDF15 treatment in mice counteracts compensatory reductions in energy expenditure, resulting in greater weight loss and reductions in non-alcoholic fatty liver disease compared to caloric restriction alone.
Mice Gfral-null mice were generated as described previously32 and breeding pairs were provided by R. Seeley. The β-less mice were generated by B. Lowell as described previously51 and breeding pairs were provided J. Wu. Studies in mice were carried out at three sites (McMaster University, Université de Sherbrooke and Novo Nordisk). All of the animals used in the study were housed and cared for in accordance with the local guidelines for animal use, and studies were approved by the Animal Ethics Research Board of McMaster University (AUP: 210104), Université de Sherbrooke (2021–3001) and Danish Animal Experiments Inspectorate (2020-15-0201-00756:C01). All of the mice were group-housed on a 12 h–12 h light–dark cycle with ad libitum access to food and water. All of the mice used were males on the C57BL/6J background. All of the mice were housed in either the Solace Zone Heated IVC 32-Cage (Alternative Design Manufacturing & Supply) with HEPA filtered ventilation and temperature-regulated cages kept at 21 or 29 °C or in specific-pathogen free microisolators in a room kept at 21 or 29 °C. Before treatment with GDF15, mice were fed a high-fat, high-fructose diet (NASH Diet: 40 kcal% fat (mostly palm oil), 20 kcal% fructose and 0.02% cholesterol) (Research Diets, D19101102; for experiments performed at McMaster and Sherbrooke University) or western diet (Research Diets, D12079B; for experiments performed at Novo Nordisk). The mice used in chronic experiments at McMaster University were placed on a NASH diet and housed under thermoneutral conditions (~29 °C, 12 h–12 h light–dark cycle) or ambient temperature (~21 °C, 40–60% relative humidity) at 8 weeks of age. Mice at Novo Nordisk were placed on a housing condition (~29–30 °C, 12 h–12 h light–dark cycle) when treatment with GDF15. Before treatment, mice were randomized and separated into different treatment groups matched on body weight and composition, and single-housed. Recombinant GDF15 (Novo Nordisk, 0247-0000-0001;…
Wang, Centre For Metabolism, Obesity, Diabetes Research, Mcmaster University, Hamilton, Division Of Endocrinology, Metabolism, Department Of Medicine, Townsend