Gallic acid (GA) is a simple
polyphenol found in food and
traditional Chinese medicine. Here, we determined the effects of GA administration in a combined mouse model of high-fat diet (HFD)-induced
obesity and low-dose
streptozotocin (STZ)-induced
hyperglycemia, which mimics the concurrent
non-alcoholic fatty liver disease (
NAFLD) and
type 2 diabetes pathological condition. By combining the results of physiological assessments, pathological examinations, metabolomic studies of blood, urine, liver, and muscle, and measurements of gene expression, we attempted to elucidate the efficacy of GA and the underlying mechanism of action of GA in hyperglycemic and dyslipidemic mice. HFD and STZ induced severe diabetes,
NAFLD, and other metabolic disorders in mice. However, the results of liver histopathology and serum biochemical examinations indicated that daily GA treatment alleviated the high
blood glucose levels in the mice and decelerated the progression of
NAFLD. In addition, our results show that the hepatoprotective effect of GA in diabetic mice occurs in part through a partially preventing disordered metabolic pathway related to
glucose,
lipids,
amino acids,
purines, and
pyrimidines. Specifically, the mechanism responsible for alleviation of
lipid accumulation is related to the upregulation of β-oxidation and ketogenesis. These findings indicate that GA alleviates
metabolic diseases through novel mechanisms.