Traditional Chinese Medicine Formula Boosts GLP-1 to Combat Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD) affects 25-30% of adults globally and is strongly linked to insulin resistance and metabolic dysfunction. This study investigated how Ge-Lian Qi-Shen decoction (GQD), a nine-herb traditional Chinese medicine formula, combats NAFLD through novel mechanisms involving GLP-1 hormone regulation.

Researchers used C57BL/6J mice fed a high-fat diet to model NAFLD, then treated them with different doses of GQD for 4-8 weeks. They employed comprehensive analyses including biochemical tests, glucose tolerance assessments, gut microbiome sequencing, and cell culture studies to understand GQD's mechanisms of action.

GQD demonstrated dose-dependent improvements in hepatic steatosis, glucose tolerance, and blood lipid levels while increasing serum GLP-1 levels and reducing energy intake. The formula works through dual pathways: specific compounds like berberine, coptisine, and nuciferine directly activate bitter taste receptors and TGR5 in intestinal endocrine cells, promoting immediate GLP-1 secretion. Simultaneously, GQD reshapes gut microbiota composition, increasing beneficial bacteria like Muribaculaceae and Akkermansia, which produce short-chain fatty acids (acetate, propionate, butyrate, valerate) that activate fatty acid receptors and sustain GLP-1 production.

Fecal microbiota transplantation experiments confirmed that gut microbiome changes partially mediate GQD's therapeutic effects. The study identified 24 bioactive compounds in GQD and demonstrated that alkaloids, anthraquinones, and triterpenoids contribute to its anti-NAFLD activity through G-protein-coupled receptor activation.

These findings reveal how traditional herbal medicine can target modern metabolic diseases through sophisticated multi-pathway mechanisms, offering potential new approaches for NAFLD treatment that combine direct pharmacological effects with beneficial microbiome modulation.