Institute of Metabolic and Cardiovascular Diseases, INSERM/Paul Sabatier University, UMR1297, Toulouse, France.
School of Health and Human Performance, Dublin City University, Dublin, Ireland.
Cell Rep. 2024 Aug 27;43(8):114577. doi: 10.1016/j.celrep.2024.114577. Epub 2024 Aug 2.
Growth and differentiation factor 15 (GDF15) has recently emerged as a weight loss and insulin-sensitizing factor. Growing evidence also supports a role for GDF15 as a physiological, exercise-induced stress signal. Here, we tested whether GDF15 is required for the insulin-sensitizing effects of exercise in mice and humans. At baseline, both under a standard nutritional state and high-fat feeding, GDF15 knockout (KO) mice display normal glucose tolerance, systemic insulin sensitivity, maximal speed, and endurance running capacity when compared to wild-type littermates independent of sex. When submitted to a 4-week exercise training program, both lean and obese wild-type and GDF15 KO mice similarly improve their endurance running capacity, glucose tolerance, systemic insulin sensitivity, and peripheral glucose uptake. Insulin-sensitizing effects of exercise training were also unrelated to changes in plasma GDF15 in humans. In summary, we here show that GDF15 is dispensable for the insulin-sensitizing effects of chronic exercise.
生长分化因子 15（GDF15）最近被认为是一种减肥和胰岛素增敏因子。越来越多的证据也支持 GDF15 作为一种生理性、运动诱导的应激信号的作用。在这里，我们测试了 GDF15 是否是运动对小鼠和人类产生胰岛素增敏作用所必需的。在基线时，无论是在标准营养状态还是高脂肪喂养下，GDF15 敲除（KO）小鼠与野生型同窝仔相比，在性别无关的情况下，均表现出正常的葡萄糖耐量、全身胰岛素敏感性、最大速度和耐力跑步能力。当进行为期 4 周的运动训练计划时，无论是瘦型还是肥胖型野生型和 GDF15 KO 小鼠，均能相似地提高其耐力跑步能力、葡萄糖耐量、全身胰岛素敏感性和外周葡萄糖摄取。运动训练的胰岛素增敏作用也与人类血浆 GDF15 的变化无关。总之，我们在这里表明，GDF15 对于慢性运动的胰岛素增敏作用是可有可无的。
