Impact of Reducing Visceral Adipose During ‘Menopausal’ Weight Gain on the Mammary Tumor Microenvironment in Mouse Model of Obesity & Breast Cancer
Description
Objective: Menopause and ovarian function loss via ovariectomy (OVX) both lead to increased visceral adiposity (VAT), which contributes to chronic inflammation and elevated breast cancer risk1,2. In particular, crown-like structures (CLS) in the mammary gland reflect macrophage infiltration and are associated with obesity-related tumor progression3. Preventing weight gain after OVX in rodents has been shown to reduce VAT, adipocyte size, macrophage infiltration, and tumor burden4. We hypothesize that removing VAT at the time of OVX would reduce mammary CLS and adipocyte size, and ultimately tumor burden in a breast cancer mouse model.
Approach: Female C57BL/6 mice were fed a 40% high-fat diet and underwent OVX with or without VAT lipectomy. Macrophage infiltration was assessed by immunofluorescence staining for macrophages (Mac2 (Galectin-3)) and adipocyte membranes (Caveolin-1). Mean Mac2-positive area was quantified using QuPath. Adipocyte cellularity was quantified in H&E stained slides using the Adiposoft plugin in Fiji.
Results: VAT lipectomy did not significantly impact macrophage infiltration, as measured by percent Mac2-positive area (1.43% vs. 3.29%, p = 0.318); this difference was further reduced after outlier removal from the controls (1.43% vs. 1.57%, p = 0.78). VAT lipectomy decreased the proportion of large adipocytes and tended to reduce mean adipocyte area versus controls. (1014 μm² vs. 1190 μm², p = 0.088). While not statistically significant, these findings suggest that a reduction in VAT may modestly reduce adipocyte hypertrophy in mammary adipose tissue, but mechanisms remain to be identified.
Conclusions: In OVX mice, VAT lipectomy modestly reduced adipocyte size but did not lessen mammary adipose macrophage infiltration, suggesting that VAT reduction may affect tumor burden through mechanisms beyond local inflammation. Ongoing work is aimed at understanding the influence of visceral adiposity on the tumor microenvironment.
Citation Information
Yang, Jimmy; Kucinskas, Amanda; Gibson, Charlotte; and Giles, Erin D., "Impact of Reducing Visceral Adipose During ‘Menopausal’ Weight Gain on the Mammary Tumor Microenvironment in Mouse Model of Obesity & Breast Cancer" (2026). Office of Research DMU Research Symposium. 56.
https://digitalcommons.dmu.edu/researchsymposium/2025rs/2025abstracts/56
Impact of Reducing Visceral Adipose During ‘Menopausal’ Weight Gain on the Mammary Tumor Microenvironment in Mouse Model of Obesity & Breast Cancer
Objective: Menopause and ovarian function loss via ovariectomy (OVX) both lead to increased visceral adiposity (VAT), which contributes to chronic inflammation and elevated breast cancer risk1,2. In particular, crown-like structures (CLS) in the mammary gland reflect macrophage infiltration and are associated with obesity-related tumor progression3. Preventing weight gain after OVX in rodents has been shown to reduce VAT, adipocyte size, macrophage infiltration, and tumor burden4. We hypothesize that removing VAT at the time of OVX would reduce mammary CLS and adipocyte size, and ultimately tumor burden in a breast cancer mouse model.
Approach: Female C57BL/6 mice were fed a 40% high-fat diet and underwent OVX with or without VAT lipectomy. Macrophage infiltration was assessed by immunofluorescence staining for macrophages (Mac2 (Galectin-3)) and adipocyte membranes (Caveolin-1). Mean Mac2-positive area was quantified using QuPath. Adipocyte cellularity was quantified in H&E stained slides using the Adiposoft plugin in Fiji.
Results: VAT lipectomy did not significantly impact macrophage infiltration, as measured by percent Mac2-positive area (1.43% vs. 3.29%, p = 0.318); this difference was further reduced after outlier removal from the controls (1.43% vs. 1.57%, p = 0.78). VAT lipectomy decreased the proportion of large adipocytes and tended to reduce mean adipocyte area versus controls. (1014 μm² vs. 1190 μm², p = 0.088). While not statistically significant, these findings suggest that a reduction in VAT may modestly reduce adipocyte hypertrophy in mammary adipose tissue, but mechanisms remain to be identified.
Conclusions: In OVX mice, VAT lipectomy modestly reduced adipocyte size but did not lessen mammary adipose macrophage infiltration, suggesting that VAT reduction may affect tumor burden through mechanisms beyond local inflammation. Ongoing work is aimed at understanding the influence of visceral adiposity on the tumor microenvironment.
