Dietary Betaine Improves Glucose Metabolism in Obese Mice.

BACKGROUND: Obesity caused by the overconsumption of energy-dense foods high in fat and sugar has contributed to the growing prevalence of type 2 diabetes (T2D). Betaine found in food or supplement has been found to lower blood glucose levels, but its exact mechanism of action is not well understood.

OBJECTIVE: A comprehensive evaluation of the potential mechanisms by which betaine supplementation improves glucose metabolism.

METHODS: Hyperglycemic mice were fed betaine to measure the indexes of glucose metabolism in the liver and muscle. To explore the mechanism behind the regulation of betaine on glucose metabolism, RNA-seq was used to analyze the livers of the mice. In vitro, HepG2 and C2C12 cells were treated with betaine to more comprehensively evaluate the effect of betaine on glucose metabolism.

RESULTS: Betaine was added to the drinking water of high-fat diet-induced mice and it was found to reduce blood glucose levels and liver triglyceride (TG) levels without affecting body weight, confirming its hypoglycemic effect. To investigate the specific mechanism underlying its hypoglycemic effect, protein-protein interaction (PPI) enrichment analysis of the liver revealed key nodes associated with glucose metabolism, including cytochrome P450 family activity, insulin sensitivity, glucose homeostasis, and TG levels. The Kyoto encyclopedia of genes and genomes (KEGG) and gene ontogeny (GO) enrichment analyses showed significant enrichment of the Notch signaling pathway. These results provided bioinformatic evidence for specific pathways through which betaine regulates glucose metabolism. Key enzyme activities involved in glucose uptake, glycogen synthesis and glycogenolysis pathways of liver and muscle were measured and improvements were observed in these pathways.

CONCLUSIONS: This study provides new insight into the mechanisms by which betaine improves glucose metabolism in the liver and muscle and supports its potential as a drug for the treatment of metabolic disorders related to glucose.