Davezac Morgane, Buscato Mélissa, Zahreddine Rana, Darnaud Faustine, Auriol Pauline, Adlanmerini Marine, Gourdy Pierre, Arnal Jean-François, Lenfant Françoise, Fontaine Coralie
Inserm U1297 (I2MC), CHU de Toulouse and Université Toulouse, Avenue Jean Poulhes, CHU Rangueil, 31432, Toulouse, France.
Sci Rep. 2025 Aug 26;15(1):31326. doi: 10.1038/s41598-025-13662-4.
Growth Differentiation Factor 15 (GDF15) is recognized as a biomarker of cardiovascular disease, but its role in atherosclerosis remains unclear. Here, we investigated the role of GDF15 in atherosclerosis by crossing GDF15-deficient mice with LDLr mice. Male GDF15 LDLr mice fed a Western diet developed less atherosclerotic lesions than littermate controls despite exhibiting a pro-obesogenic phenotype, whereas GDF15 deficiency did not affect metabolism or lesion development in females. Plasma GDF15 levels were higher in male LDLr mice than in females but were comparable to those measured in ovariectomized LDLr females. Importantly, ovariectomy in females induced metabolic and vascular phenotypes similar to those of GDF15 LDLr males, while gonadectomy in males had no effect, emphasizing the role of female steroid hormones in GDF15-related sexual dimorphism. These findings highlight the sex-specific effects of GDF15 on metabolism and atherosclerosis, underscoring the importance of sex and hormonal status in cardiometabolic disease management.
生长分化因子15（GDF15）被认为是心血管疾病的生物标志物，但其在动脉粥样硬化中的作用仍不清楚。在这里，我们通过将GDF15基因缺陷小鼠与LDLr小鼠杂交，研究了GDF15在动脉粥样硬化中的作用。尽管雄性GDF15 LDLr小鼠表现出促肥胖表型，但喂食西式饮食的雄性GDF15 LDLr小鼠比同窝对照小鼠形成的动脉粥样硬化病变更少，而GDF15基因缺陷对雌性小鼠的代谢或病变发展没有影响。雄性LDLr小鼠血浆GDF15水平高于雌性，但与去卵巢LDLr雌性小鼠测得的水平相当。重要的是，雌性小鼠去卵巢会诱导出与GDF15 LDLr雄性小鼠相似的代谢和血管表型，而雄性小鼠去势则没有影响，这强调了雌性甾体激素在GDF15相关性别二态性中的作用。这些发现突出了GDF15对代谢和动脉粥样硬化的性别特异性影响，强调了性别和激素状态在心脏代谢疾病管理中的重要性。
