(P20-026-25) HPA Axis Suppressing Immunotherapy Induces Quality Weight Loss Across Male and Female Monogenic Mouse Models of Obesity

Objectives: The anti-corticotropin releasing factor (anti-CRF) CTRND05 antibody effectively alters body composition and induces weight loss in DIO mouse models. In this study, we investigated the effects of anti-CRF in monogenic mouse models of obesity.

Methods: Lep ob/ob and MC4R KO male and/or female mice (homozygous, n= 6-9 per group) were age-matched at 15 weeks and maintained on a regular chow diet. Anti-CRF or anti-IgG1 was weekly injected intraperitoneally for 12 - 18 weeks. The obesity phenotypes of the mice were evaluated.

Results: Irrespective of genetic background and sex, CTRND05-treated mice gained 15-35% less body weight, increased muscle mass by 5 – 12%, and reduced fat mass by 5 –10% compared to the IgG1-treated control. In addition, CTRND05 increased relative brain mass, and muscle strength while decreasing plasma insulin, glucagon, FGF-21, and corticosterone. It also increased glucose clearance except in male leptin ob/ob mice.

Conclusions: Our data suggest that anti-CRF treatment mitigates obesity phenotypes in hypothalamic-driven forms of monogenic obesity, highlighting anti-CRF’s therapeutic potential for obesity management.

Funding Sources: NIH and The Goizueta Institute funded this project.