Weight loss increases adipose macrophage cytokine and ROS production, which correlates with lower adipose Staphylococcus aureus after systemic infection in male mice

Innate immune memory forms in macrophages to a myriad of stimuli that enhances their responsiveness to subsequent stimuli. We previously showed that weight loss (prior obesity) induces adipose macrophage innate immune memory that increases inflammatory activation and correlates with worsened diabetes risk after weight regain. However, any effect of weight loss-induced innate immune memory on anti-microbial defenses are not known. We hypothesized that weight loss would broadly increase adipose macrophage function and reduce bacterial burden in a mouse model of infection. Male C57Bl/6J mice were put on high-fat or low-fat diets over 18 weeks to induce lean, weight gain, or weight loss groups. We found that weight loss increased cytokine production in response to the bacterial product lipoteichoic acid and increased ROS production. There was no effect on phagocytosis. Mice from each group were then infected intravenous with 2.5x10^8 colony forming units Staphylococcus aureus. Temperature and body condition score were recorded twice daily and tissues were collected at day 3. Weight gain mice had the lowest body temperature, highest body condition scores, highest blood neutrophils, and the highest bacterial burden in the kidney. The weight loss group had the lowest adipose bacterial burden and the highest adipose macrophage cytokine production. Thus, weight loss-induced adipose macrophage memory may help mitigate local S. aureus infection. Collectively, these findings together with our previous work support the notion that innate immune memory is an evolutionarily protective mechanism against infection that also contributes to the development of cardiometabolic diseases. To HC: Vanderbilt Infection, Inflammation, and Immunology Mini-Sabbatical Grant and a UH CLASS Research Project Grant. To JB: NIGMS R35 (5R35GM141927) This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.