Tumor Biology

ORF24-01 - Tirzepatide Improves Metabolic Health and Decreases Mammary Tumor Susceptibility in High-Fat Diet-Fed Brca1 +/- Mice

Sunday, June 14, 2026

9:30 AM - 9:35 AM CT

Location: Room W180

Co-Author(s)

LQ

Linlan Qiao, B.Med

University of Kansas Medical Center
Kansas City, United States
sp

sailesh palikhe, PhD (he/him/his)

Postdoctoral Fellow
UNIVERSITY OF KANSAS MEDICAL CENTER
Kansas City, KS, United States
CK

Caleb Kutz, BS

University of Kansas Medical Center
Kansas City, United States
XL

Xiaobo Liang, BS

University of Kansas Medical Center
Kansas City, United States
JT

John Thyfault, PhD

University of Kansas Medical Center
Kansas City, United States

Senior Author/Primary Investigator(s)

KB

Kristy A. Brown, PhD

Professor of Metabolism and Cancer, Department of Cell Biology & Physiology, KUMC
UNIVERSITY OF KANSAS MEDICAL CENTER
Kansas City, KS, United States

Rapid and Poster Presenter(s)

SP

Sailesh Palikhe, PhD

UNIVERSITY OF KANSAS MEDICAL CENTER
Kansas City, United States

Co-Author(s)

PB

Priya Bhardwaj, PhD

Weill Cornell Medicine
New York, United States

Tirzepatide, a dual agonist of glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptors, induces significant weight loss and improves metabolic health in individuals with obesity and type 2 diabetes. Preclinical studies show that tirzepatide improves high-fat diet (HFD)-induced obesity, glucose intolerance, insulin sensitivity, and hepatic steatosis. Recent studies have shown that obesity and metabolic dysfunction are strongly associated with increased breast cancer risk, including in BRCA1 mutation carriers. We previously demonstrated that HFD-induced obesity exacerbates DNA damage in the mammary epithelium and accelerate 7,12-dimethylben[a]anthracene (DMBA)/medroxyprogesterone acetate (MPA)-induced mammary tumor development in Brca1 heterozygous knockout (Brca1+/-) mice compared with a low-fat diet (LFD).
In this study, we hypothesized that tirzepatide treatment would attenuate metabolic dysfunction and delay or prevent mammary tumor development in HFD-fed female Brca1+/- mice by reducing DNA damage in the mammary epithelium. We found that tirzepatide-treated HFD-fed Brca1+/-mice exhibited significant reductions in body weight gain, fat mass, and food intake compared with vehicle-treated controls. Tirzepatide also improved glucose tolerance and markedly reduced hepatic steatosis. Importantly, tirzepatide treatment reduced DNA damage in mammary epithelial cells of HFD-fed Brca1+/- mice. The DMBA/MPA-induced mammary tumor study is ongoing. Preliminary observations indicate higher tumor incidence in HFD-fed Brca1+/- mice compared with LFD-fed mice, with a trend toward reduced tumor incidence in tirzepatide-treated HFD-fed mice. These findings suggest that tirzepatide-mediated improvements in metabolic health are associated with reduced mammary epithelial DNA damage and may influence mammary tumor susceptibility in BRCA1 mutation carriers.