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Growth differentiation factor 15 neutralization does not impact anorexia or survival in lipopolysaccharide-induced inflammation

2021; Cell Press; Volume: 24; Issue: 6 Linguagem: Inglês

10.1016/j.isci.2021.102554

2589-0042

Danna M. Breen, Srinath Jagarlapudi, Anita Patel, Chang Zou, Stephanie Joaquim, Xiangping Li, Liya Kang, Jincheng Pang, Katherine Hales, Enida Ziso-Qejvanaj, Nicholas B. Vera, Donald Bennett, Tao He, Matthew Lambert, Kerry Kelleher, Zhidan Wu, Bei B. Zhang, Laura Lin, Randy J. Seeley, Olivier Bézy,

Macrophage Migration Inhibitory Factor

Growth differentiation factor 15 (GDF15) causes anorexia and weight loss in animal models, and higher circulating levels are associated with cachexia and reduced survival in cancer and other chronic diseases such as sepsis. To investigate the role of sepsis-induced GDF15, we examined whether GDF15 neutralization via a validated and highly potent monoclonal antibody, mAB2, modulates lipopolysaccharide (LPS)-induced anorexia, weight loss, and mortality in rodents. LPS injection transiently increased circulating GDF15 in wild-type mice, decreased food intake and body weight, and increased illness behavior and mortality at a high dose. GDF15 neutralization with mAB2 did not prevent or exacerbate any of the effects of LPS. Similarly, in GDF15 knockout mice, the LPS effect on appetite and survival was comparable with that observed in wild-type controls. Therefore, effective inhibition of circulating active GDF15 via an antibody or via gene knockout demonstrated that survival in the LPS acute inflammation model was independent of GDF15.