Coniferaldehyde ameliorates the lipid and glucose metabolism in palmitic acid-induced HepG2 cells via the LKB1/AMPK signaling pathway

Impaired lipid and glucose metabolism in the liver is a crucial characteristic of nonalcoholic fatty liver disease (NAFLD). Coniferaldehyde (CA), a kind of phenolic compound found in many edible plants, has multiple biological and pharmacological functions. However, since the effect and molecular mechanism of CA on hepatic lipid and glucose metabolism disorders in NAFLD remain unknown, this study investigated its impact on the lipid and glucose metabolism of palmitic acid (PA)-induced HepG2 cells. Compared with the HepG2 cells treated only with PA, supplementation with 25, 50, and 100 mu M CA reduced the levels of intracellular triglyceride (by 7.11%, 19.62%, and 31.57%) and total cholesterol (by 8.46%, 23.32%, and 27.17%), and enhanced glucose uptake (by 40.91%, 57.49%, and 61.32%) and intracellular glycogen content (by 12.75%, 41.27%, and 53.77%). Moreover, CA supplementation downregulated the expression of sterol regulatory element-binding protein-1, fatty acid synthase, and stearoyl-CoA desaturase 1 related to lipogenesis while upregulating the expression of carnitine palmitoyltransferase 1 alpha related to fatty acid oxidation. CA supplementation also upregulated the glucose transporter 2 protein expression and phosphorylation of glycogen synthase kinase 3 beta while downregulating the phosphorylation of glycogen synthase. Most importantly, most of these effects of CA were reversed by pretreatment with AMP-activated protein kinase (AMPK) inhibitor and small interfering RNA-liver kinase B1 (LKB1). In conclusion, CA ameliorated the lipid and glucose metabolism in PA-induced HepG2 cells via the LKB1/AMPK signaling pathway. Practical Application In this study, coniferaldehyde appeared to be effective in ameliorating hepatic lipid and glucose metabolism disorders in nonalcoholic fatty liver disease by reducing the levels of intracellular triglyceride and total cholesterol and enhancing glucose uptake and intracellular glycogen content via the LKB1/AMPK signaling pathwayin vitro. Therefore, our findings provide new evidence in support of that supplementation with coniferaldehyde or food rich in coniferaldehyde might be considered as a viable dietary intervention strategy for preventing and treating nonalcoholic fatty liver disease.