Western Diet-Induced Obesity Modulates the Mammary Fat Pad Microenvironment

Area of Science:

• * Investigating the complex interplay between diet, obesity, and the mammary gland microenvironment.
• * Focusing on the physiological and immunological changes within the mammary fat pad microenvironment (MFPME).

Background:

• * Obesity is a known risk factor for postmenopausal breast cancer, linked to increased tumor growth.
• * The specific impact of obesity on the mammary fat pad microenvironment (MFPME) is not well understood.
• * Dietary patterns, such as the Western Diet (WD), are implicated in obesity and metabolic changes.

Purpose of the Study:

• * To investigate the effects of a Western Diet (WD) on the mammary fat pad microenvironment (MFPME) in immunocompetent female mice.
• * To analyze changes in immune cell infiltration and gene expression within the MFPME.

Main Methods:

• * Utilized immunocompetent female mice fed a Western Diet (WD).
• * Analyzed tissue weights (body, liver, perigonadal white adipose tissue - pWAT) and immune cell infiltration.
• * Employed NanoString and RNA-Sequencing (RNA-Seq) to assess gene expression and cellular processes in the MFPME.

Main Results:

• * The WD significantly increased body, liver, and pWAT weight, alongside myeloid cell infiltration.
• * No significant changes were observed in CD4+ and CD8+ T cell populations in the liver, blood, or pWAT.
• * Upregulation of immune-related pathways (complement system, innate immunity, phagocytosis, immune metabolism, NLR signaling) was detected in the MFPME of obese mice.
• * RNA-Seq revealed significant modulation of MFPME physiology via gene expression, cellular processes, and signaling pathways.

Conclusions:

• * The Western Diet induces obesity and alters the mammary fat pad microenvironment (MFPME) in mice.
• * MFPME changes involve increased myeloid infiltration and altered immune signaling pathways.
• * Further research is needed to elucidate how WD-induced MFPME modifications influence breast cancer biology.