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

Abstract

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 µM 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 1α related to fatty acid oxidation. CA supplementation also upregulated the glucose transporter 2 protein expression and phosphorylation of glycogen synthase kinase 3β 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 pathway in 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.

γ-Linolenic Acid Prevents Lipid Metabolism Disorder in Palmitic Acid-Treated Alpha Mouse Liver-12 Cells by Balancing Autophagy and Apoptosis via the LKB1-AMPK-mTOR Pathway

“…3 As recently reported, 200 μM PA markedly increased TG and TC contents by 70.07 and 75.21% in HepG2 cells, respectively. 16 This study created a high-fat model of AML-12 with 400 μM PA (for 24 h), which significantly induced lipid deposition, as indicated by increases in TG and TC contents. A previous study reported that GLA could reduce concentrations of TG, TC, and β-lipoprotein in mouse plasma, with efficiencies of up to 81.5, 68.2, and 64.8%, respectively.…”

“…13,47 LKB1 is an upstream kinase, which can regulate autophagy by phosphorylating AMPK. In hepatocytes, PA treatment markedly decreased pLKB1/LKB1 and p-AMPK/AMPK protein expressions, 16 while PUFAs can increase LKB1 protein expression and promote AMPKα phosphorylation. 48 n-6 PUFAs increased AMPK activity and activated autophagy through TOR-independent signaling pathways.…”

Coniferyl aldehyde alleviates LPS-induced WI-38 cell apoptosis and inflammation injury via JAK2–STAT1 pathway in acute pneumonia

“…9 Moreover, CA was reported to ameliorate glucose and lipid metabolism in HepG2 by LKB1/AMPK. 10 In addition, CA was also reported to prevent destruction of articular cartilage in a murine model by Nrf2/HO-1. 11 Another novel discovery of this study was that JAK2 and STAT1 proteins were the targets of CA.…”

Astragaloside IV ameliorates fat metabolism in the liver of ageing mice through targeting mitochondrial activity

“…AMPK is an important regulator of hepatic lipid metabolism, which can enhance insulin sensitivity and fatty acid oxidation. 33 Our results showed that AST administration could significantly enhance the expression of pAMPK in the liver of ageing mice (Figure 3 ), indicating that AST can activate AMPK in the liver. ACC1 is the downstream target of AMPK and can catalyse the production of malonyl‐CoA.…”

“…AST administration can significantly reduce the ratio of liver weight to body weight and reduce hepatic TG content (Figure 1), indicating that the liver plays an important role in AST‐mediated regulation of lipid metabolism. AMPK is an important regulator of hepatic lipid metabolism, which can enhance insulin sensitivity and fatty acid oxidation 33 . Our results showed that AST administration could significantly enhance the expression of pAMPK in the liver of ageing mice (Figure 3), indicating that AST can activate AMPK in the liver.…”