Abstract

Abstract ‘Crown-like structures’ (CLS) of CD68+ macrophages in human subcutaneous, visceral and breast adipose depots associate with cardiometabolic and cancer risks. Rather than surgical fat biopsy, which is difficult for vulnerable humans, informative blood-based assays are preferred for medical decision making and risk assessment. HYPOTHESIS. Breast CLS and adipocyte parameters, as measures of metabolic health, meaningfully associate with pro-inflammatory imbalances of specific cytokines and adipokines in plasma of obese women. RESULTS. We obtained breast histological samples and matched plasma of 20 obese, unhealthy African American women in the Komen Tissue Bank and the Black Women’s Health Study, and compared to 20 age-, sex- and race-matched subjects who were obese but healthy; and to a matched cohort who were lean and healthy. We measured 41 cytokines and adipokines in plasma, and determined CLS and adipocyte size (a measure of metabolic health) in breast fat. We used clinical determinations of cardiometabolic status as independent variables and evaluated patterns of cytokine expression and tissue immunometabolism as dependent variables. We found that obese and healthy women clearly resolve from obese and unhealthy as well as from lean and healthy, and that a limited set of cytokines and adipokines are sufficient to define risk cross-sectionally. IMPACT. Immunometabolic profile of patient plasma may offer a robust tool to assist patient-provider discussion of risk.

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