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

Authors :
Breen DM
Jagarlapudi S
Patel A
Zou C
Joaquim S
Li X
Kang L
Pang J
Hales K
Ziso-Qejvanaj E
Vera NB
Bennett D
He T
Lambert M
Kelleher K
Wu Z
Zhang BB
Lin L
Seeley RJ
Bezy O
Source :
IScience [iScience] 2021 May 19; Vol. 24 (6), pp. 102554. Date of Electronic Publication: 2021 May 19 (Print Publication: 2021).
Publication Year :
2021

Abstract

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.<br />Competing Interests: R.J.S. is a member of the advisory boards of Novo Nordisk, Scohia, Kintai Therapeutics, and Ionis. D.M.B., S.J., C.Z., S.J., X.L., L.K., J.P., K.H., E.Z.Q., D.B., M.L., K.K., Z.W., B.B.Z., and L.L. are employees and shareholders of Pfizer. N.B.V., T.H., and O.B. were employees of Pfizer during the conduct of the study and are current employees of Dicerna Pharmaceuticals, Inc., JOINN Biologics, and Cellarity, respectively. A.P. declares no conflict of interest.<br /> (© 2021 Elsevier Inc.)

Details

Language :
English
ISSN :
2589-0042
Volume :
24
Issue :
6
Database :
MEDLINE
Journal :
IScience
Publication Type :
Academic Journal
Accession number :
34189431
Full Text :
https://doi.org/10.1016/j.isci.2021.102554