1641-P: Effect of Specific Weight-Reducing Interventions on Metabolic and Immunological Outcomes in Mice

Introduction & Objective: Obesity leads to glucose intolerance and immune cell alterations in different organs. Nevertheless, it remains unknown whether these metabolic and immunological changes are reversible following weight loss and if they differ with specific weight-reducing interventions. This study aimed to address whether obesity-associated metabolic and immunological changes are reversed after weight loss, comparing the effects of caloric restriction versus switch to a healthier diet.

Methods: Male C57Bl/6j mice were fed high fat diet (HFD), and randomized after 8 weeks into the following groups: continued HFD, HFD combined with caloric restriction or switched back to standard diet (HFD/SD), while an additional group was on SD throughout the experiment. Metabolic parameters were assessed at distinct timepoints and immune cells characterized by flow cytometry at the end of the experiment.

Results: The body weights of mice on SD, HFD/caloric restriction and HFD/SD were comparable from two weeks after the intervention onwards, while HFD fed mice had higher body weights. Initially, both HFD/caloric restriction and HFD/SD mice showed similar improvements in glucose tolerance and insulin secretion compared to mice on SD. However, glucose tolerance deteriorated over time in mice on HFD/caloric restriction, while their insulin levels remained low. Weight loss correlated with a decrease in inflammatory adipose tissue macrophages (ATMs), an increase in anti-inflammatory ATMs and eosinophils in AT, colon and liver. Colon B-cells decreased only in HFD/SD mice, while liver neutrophils and regulatory T-cells in AT increased.

Conclusion: Independent of the weight loss strategy, weight loss is associated with a reversal of hyperinsulinemia and AT inflammation as well as increased eosinophils in various organs. In contrast, a switch from HFD to SD specifically leads to reduced B-cells in the colon and increased neutrophils in liver and regulatory T-cells in AT.