# Adiponectin receptor agonist as potential therapeutic candidate for breast cancer associated with obesity

Rawan Nehme, Jessy Aoun, Caroline Decombat, Mona Diab-Assaf, Laetitia Delort, Florence Caldefie-Chezet

► To cite this version:

Rawan Nehme, Jessy Aoun, Caroline Decombat, Mona Diab-Assaf, Laetitia Delort, et al.. Adiponectin receptor agonist as potential therapeutic candidate for breast cancer associated with obesity. 46th ESPEN Congress on Clinical Nutrition and Metabolism, Sep 2024, Milan (Italie), Italy. hal-04876098

HAL Id: hal-04876098

https://hal.science/hal-04876098v1

Submitted on 14 Jan 2025

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# Adiponectin receptor agonist as potential therapeutic candidate for breast cancer associated with obesity

P593

R. Nehme¹, J. Aoun¹, C. Decombat¹, M. Diab-Assaf², L. Delort¹ and F. Caldefie-Chézet¹

1 Université Clermont-Auvergne, INRAE, UNH, Unité de Nutrition Humaine, CRNH-Auvergne, 63000 Clermont-Ferrand, France;

2 Equipe Tumorigénèse Pharmacologie Moléculaire et Anticancéreuse, Faculté des Sciences II, Université libanaise Fanar, Lebanon;

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## Background

Obesity and breast cancer (BC) represent significant health challenges, both of which are closely linked through inflammatory processes. Obesity increases the risk of postmenopausal BC, and adipokines play a pivotal role in this relationship. Adiponectin is a bioactive molecule implicated in regulating BC development, progression, and metastases throughout different metabolic signaling pathways that could be reactivated by targeting adiponectin receptors. Adiponectin receptor agonist (ARA) could specifically replace human adiponectin, activate its receptor, mimic its function and subsequently ameliorate its anti-cancer activity on breast cancer.

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## Results

<figure><img src="image_6.png" /><figcaption>Result 1: Treatment with ARA demonstrated significant reduction in BC cell viability along with an increase in apoptosis.</figcaption></figure>

<figure><img src="image_7.png" /><figcaption>Result 2: Within the tumor adipose inflammatory microenvironment, ARA exhibited several beneficial effects.</figcaption></figure>

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## Method

1. Adipospheroids were developed from adipocyte stem cells from subcutaneous adipose tissue of obese women using Incucyte® technology with the aim of mimicking adipose tissue.

2. Effect of ARA on the viability of MCF-7 breast cancer cells and the obese inflammatory microenvironment was evaluated using a co-culture between adipospheroids, macrophages and MCF-7 breast cancer tumoroid.

(1)

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MicroTissues® 3D Petri Dish® micro-mold

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Non-adherent agarose mold

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Spheroid reach a diameter of 350-400 µm

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Incucyte®

(2)

MCF7 tumoroids

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Adipospheroids

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Macrophages M1

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+/- ARA

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Collect Tumoroids RNA

Collect Adipospheroid RNA

Collect macrophages RNA

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## Summary/ Highlights

Our findings indicate that ARA may have dual effects on both obesity and breast cancer through its indirect reactivation of the anti-inflammatory and anti-tumor activity of adiponectin. Ongoing studies are underway to better explore its impact on BC development, with the intention of potentially integrating it into personalized treatment strategies for obese BC patients.

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ESPEN
The European Society for
Clinical Nutrition and Metabolism

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