AUTHOR=Caslin Heather L. , Cottam Matthew A. , Piñon Jacqueline M. , Boney Likem Y. , Hasty Alyssa H. 

TITLE=Weight cycling induces innate immune memory in adipose tissue macrophages

JOURNAL=Frontiers in Immunology

VOLUME=Volume 13 - 2022

YEAR=2023

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.984859

DOI=10.3389/fimmu.2022.984859

ISSN=1664-3224

ABSTRACT=Weight loss improves obesity-associated diabetes risk. However, most individuals regain weight, which worsens the risk of developing diabetes and cardiovascular disease. We previously reported that male mice retain obesity-associated immunological changes even after weight loss, suggesting that immune cells may remember the state of obesity. Therefore, we hypothesized that cycles of weight gain and loss, otherwise known as weight cycling, can induce innate memory in adipose macrophages. We first treated bone marrow derived macrophages in a culture model of innate immune memory. Priming the cells with palmitic acid or adipose tissue conditioned media from obese mice increased maximal glycolysis and oxidative phosphorylation and increased LPS-induced TNFα and IL-6 production. Palmitic acid effects were dependent on TLR4 and impaired by methyltransferase inhibition and AMPK activation. While weight loss improved glucose tolerance, adipose macrophages were primed for greater activation to subsequent stimulation by LPS ex vivo as measured by cytokine production. In a model of weight cycling, adipose macrophages had elevated metabolism and secreted higher levels of basal TNFα, suggesting that weight loss can also prime macrophages for heighted activation to weight regain. Together, these data suggest that weight loss following obesity can prime adipose macrophages for enhanced inflammation upon weight regain. This innate immune memory response may contribute to worsened glucose tolerance following weight cycling.