(OR19-03-24) The Vegetable Urtica Dioca Protects Against Diet-Induced Obesity Through Pathways That Are Both Dependent And Independent of The Gut Microbiota

Objectives: Diet-induced obesity is associated with several factors which include the gut microbiota and associated metabolites. We have previously shown that through mechanisms that involve gut microbiota function the vegetable Urtica dioca (UT) attenuates fat accumulation and insulin resistance due to a high-fat (HF) diet. In this follow-up study, we sought to determine whether inclusion of UT in an HF diet would be protective in the absence of gut microbiota. We hypothesized that UT imparts beneficial effects that are dependent and independent of the microbiota.

Methods: C57BL6J conventional and germ-free mice were fed an HF diet with or without 2% UT for 7-12 weeks. Changes in body weight and insulin resistance were determined. At euthanasia, fat accumulation and liver weight were determined. From adipose tissue, skeletal muscle, and liver the expression of genes involved in fat metabolism and accumulation was determined. From serum, a metabolomics analysis was performed.

Results: As expected, fat accumulation in germ-free mice was subdued compared to conventional mice fed the same HF diet. However, supplementation with UT in both conventional and germ-free mice attenuated HF diet-induced fat accumulation and insulin resistance. In germ-free mice, compared to the HF group, supplementation with UT decreased body weight, total fat pad weight, and liver weight by 13%, 45%, and 10% respectively. In conventional mice, the decrease was 23%, 23%, and 32% respectively. In germ-free mice, UT downregulated the expression of ACC1 and PParg2 genes that encode proteins involved in lipogenesis. In conventional mice, UT promoted the expression of genes involved in fat metabolism specifically, FoxO1, Adiponectin, leptin receptors, and PGC-1𝛼. Ongoing metabolomics analysis of serum showed a 4-fold decrease in 4-Hydroxyquinoline in conventional mice supplemented with UT. This kynurenine pathway metabolite is associated with inflammation and obesity.

Conclusions: Bioactive compounds in UT attenuate diet-induced obesity through pathways that are both dependent and independent of the gut microbiota.

Funding Sources: USDA–NIFA, Maryland Agricultural Experimental Station (MAES)