"Adipose Macrophage Microbial Responses Improve with Weight Loss" by McArthur Bolden III, Xenia D. Davis et al.
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Abstract

Innate immune cells can develop memory-like qualities from an initial stimulus, which enhances their effector functions to a secondary challenge. Based on the initial stimuli, innate immune memory has been shown to improve pathogen defense or worsen chronic metabolic disease. We have previously shown that weight loss induces innate immune memory which may worsen diabetes risk following weight regain. However, it is not clear if weight loss induces any protection in infection. PURPOSE: The purpose of this study was to investigate the effect of diet-induced weight gain and loss on survival, bacterial clearance, and macrophage activation in a mouse model of infection. METHODS: Male C57BL/6J mice were placed on 9-week cycles of low-fat or high-fat diets for a total of 18 weeks to elicit lean, weight gain, or weight loss groups. At 18 weeks, all mice were inoculated intravenously with 2.5x10^8 CFU of Staphylococcus aureus. Tissues were collected from 10 mice/group at day 3 and the remaining mice were followed for survival. RESULTS: There was no difference in survival between lean, weight gain, and weight loss groups (p=0.172). However, weight gain mice had significantly elevated blood neutrophils (p<0.05) and bacterial burden in the kidney (p<0.05). Weight loss mice had significantly elevated plasma TNF-a (p<0.05) and adipose macrophage cytokine production (p<0.01) that correlated with increased bacterial clearance in adipose tissue (p<0.05). CONCLUSION: Thus, we conclude that weight loss- induced innate memory and the associated cytokine production may improve local pathogen, or anti-microbial, defense.

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