(P03-019-23) Urtica dioica Whole Vegetable Attenuates Diet-Induced Obesity via Mechanisms Involving Fat Absorption and Immune Cell Function in the Small Intestines

Objectives: Urtica dioica has been studied for a wide range of health benefits due to its rich phytochemical components. In a previous study, we have shown that supplementation of a high-fat (HF) diet with U. dioica whole vegetable attenuates fat accumulation and insulin resistance. Furthermore, it enhances gut microbial diversity and specifically increases the representation of the genus Clostridium. The abundance of this taxon is associated with lower body weight and activation of intestinal regulatory T cells (Tregs). In this follow-up study, our objective was to determine the effect of dietary U. dioica on (i) extend of nutrient absorption in the small intestine and (ii) the phenotype and secretions of small intestinal immune cells.

Methods: Seven-week-old C57BL/6J mice were fed a low-fat (10% fat) diet or an HF (45% fat) diet with or without supplementation with 2% U. dioica powdered vegetable for 12 weeks. After determining anthropometric measures, enteroids were prepared from the small intestines of obese mice fed the HF diet only and were tested for the effect of U. dioica extract and metabolites from Clostridium butyricum culture on fat and glucose absorption and expression of genes involved in fat transport. The population and secretions of specific T and B cells isolated from small intestinal lamina propria were determined by flow cytometry.

Results: Supplementation of the HF diet with U. dioica attenuated weight gain, abdominal fat accumulation, and insulin resistance (p < 0.001; n = 8) compared to mice fed the HF diet only. Dietary U. dioica increased the frequency of T cells, particularly FoxP3⁺ Tregs (p < 0.05; n = 3), induced homeostatic interleukin (IL)-17-producing CD4⁺ T cells (p < 0.005; n = 3), but reduced interferon (IFN)-γ-producing CD4⁺ T cells significantly (p < 0.05; n = 3). U. dioica extract had no effect on fat absorption but metabolites of Clostridium lowered fat absorption in enteroids and reduced the expression of CD36 a protein involved in fat transport.

Conclusions: Through enhancing the representation of Clostridium, U. dioica attenuated diet-induced obesity by lowering intestinal fat absorption and promoted gut homeostasis by stimulating CD4⁺ FoxP3⁺ T cells while downregulating the IFN-γ-secreting CD4⁺ T cells.

Funding Sources: USDA-NIFA grant and Maryland Agricultural Experiment Station (MAES) grant