(PTFS08-03-24) The Effect of Broccoli Glucoraphanin Supplementation on Ameliorating High-Fat-Diet-Induced Obesity Through the Gut Microbiome and Metabolome Interface

Objectives: Obesity and its associated metabolic comorbidities pose a major global challenge for public health. Studies have shown that glucoraphanin (GRN), a natural bioactive compound enriched in broccoli, exhibits various health benefits in reversing adverse metabolic parameters. However, the precise mechanisms by which broccoli exacts its beneficial effects through the interaction between gut microbiota, metabolites, and host health outcomes remain unclear. Therefore, we interrogated the impacts of broccoli GRN supplementation on hepatocyte morphology and gut microbiome-metabolomics profiling, and how their interplay influence the process of obesity development, which is of importance for the field of obesity intervention.

Methods: The study was conducted in an obese-related C57BL/6J mouse model through the treatment of a normal control diet, high-fat diet (HFD), and HFD-GRN diet (GRN supplemented in HFD) to determine the metabolic protection of GRN in vivo. Fecal bacterial composition and serum metabolomic profiles were performed by 16S rRNA sequencing and liquid chromatography with tandem mass spectrometry (LC-MS/MS), respectively.

Results: Our study showed that HFD-GRN significantly reduced body weight and body fat accumulation leading to an improved glucose metabolism in HFD-fed animals. GRN significantly reduced lipid infiltration in the liver. Mechanistically, GRN treatment significantly altered microbial beta-diversity and composition. For example, GRN significantly increased the abundance of beneficial genera such as Mucispirillum, Enterorhabdus, and Lachnoclostridium. Furthermore, higher blood levels of L-alanine, L-proline, and Levetiracetam, but lower levels of alpha-glycerophosphate, N-acetylornithine, and ceramide compounds were observed in GRN supplemented group compared to HFD group.

Conclusions: These results indicate that GRN has a positive impact on reversing adverse metabolic parameters and reducing the risk of non-alcoholic fatty liver disease under HFD stimuli. GRN-induced microbial and metabolomic reprogramming provides mechanistic insights into the beneficial potential of GRN that further warrants GRN as a dietary intervention candidate for obesity and obesity-related abnormalities.

Funding Sources: NCCIH K01 AT009373
USDA NIFA, 2021-67017-34007