L-theanine prevents progression of nonalcoholic hepatic steatosis by regulating hepatocyte lipid metabolic pathways via the CaMKKβ-AMPK signaling pathway

Abstract

Background L-theanine, a non-protein amino acid was found principally in the green tea, has been previously shown to exhibit potent anti-obesity property and hepatoprotective effect. Herein, we investigated the effects of L-theanine on alleviating nonalcoholic hepatic steatosis in vitro and in vivo, and explored the underlying molecular mechanism. Methods In vitro, HepG2 and AML12 cells were treated with 500 μM oleic acid (OA) or treated with OA accompanied by L-theanine. In vivo, C57BL/6J mice were fed with normal control diet (NCD), high‐fat diet (HFD), or HFD along with L-theanine for 16 weeks. The levels of triglycerides (TG), accumulation of lipid droplets and the expression of genes related to hepatocyte lipid metabolic pathways were detected in vitro and in vivo. Results Our data indicated that, in vivo, L-theanine significantly reduced body weight, hepatic steatosis, serum levels of alanine transaminase (ALT), aspartate transaminase (AST), TG and LDL cholesterol (LDL-C) in HFD-induced nonalcoholic fatty liver disease (NAFLD) mice. In vitro, L-theanine also significantly alleviated OA induced hepatocytes steatosis. Mechanic studies showed that L-theanine significantly inhibited the nucleus translocation of sterol regulatory element binding protein 1c (SREBP-1c) through AMPK-mTOR signaling pathway, thereby contributing to the reduction of fatty acid synthesis. We also identified that L-theanine enhanced fatty acid β-oxidation by increasing the expression of peroxisome proliferator–activated receptor α (PPARα) and carnitine palmitoyltransferase-1 A (CPT1A) through AMP-activated protein kinase (AMPK). Furthermore, our study indicated that L-theanine can active AMPK through its upstream kinase Calmodulin-dependent protein kinase kinase-β (CaMKKβ). Conclusions Taken together, our findings suggested that L-theanine alleviates nonalcoholic hepatic steatosis by regulating hepatocyte lipid metabolic pathways via the CaMKKβ-AMPK signaling pathway.

Vitamin D improves hepatic steatosis in NAFLD via regulation of fatty acid uptake and β-oxidation

“…OA (O7501, Sigma, Germany) was conjugated to 10% (v/v) bovine serum albumin (BSA) (ST025, Beyotime, China). To induce hepatic steatosis, HepG2 cells were exposed to 0.5 mM OA for 24 h to induce lipid accumulation ( 62 – 64 ). Cells were then washed, cultured in fresh complete medium, and treated with different drugs for further analysis.…”

Regulatory Effects and Molecular Mechanisms of Tea and Its Active Compounds on Nonalcoholic Fatty Liver Disease

“…Furthermore, LTA can regulate the hepatocyte lipid metabolism pathway through the CaMKKβ (calmodulin-dependent protein kinase kinase-β)-AMPK signaling pathway, thereby alleviating nonalcoholic hepatic steatosis. 77 4.4. The Regulation of Gut Microbiota.…”

“…VTP inhibited hepatic lipogenesis by reducing the levels of SREBP1 and FAS . Moreover, LTA also could inhibit the nuclear translocation of SREBP-1c through the AMPK-mTOR signaling pathway, thereby contributing to the reduction of FA synthesis . Catechin could reduce the mRNA levels of hormone-sensitive lipase and the concentration of serum NEFA, which avoided the esterification of NEFA in the liver to generate more TG and deposit.…”

“…72 Moreover, LTA also could inhibit the nuclear translocation of SREBP-1c through the AMPK-mTOR signaling pathway, thereby contributing to the reduction of FA synthesis. 77 Catechin could reduce the mRNA levels of hormone-sensitive lipase and the concentration of serum NEFA, which avoided the esterification of NEFA in the liver to generate more TG and deposit. GTE also reversed IR by increasing insulin receptors on the cell surface, which lowered blood glucose and reduces DNL.…”

“…LTA could elevate the expression of PPARα and carnitine palmitoyltransferase-1A (CPT1A) via AMPK, and enhance fatty acid β-oxidation. Furthermore, LTA can regulate the hepatocyte lipid metabolism pathway through the CaMKKβ (calmodulin-dependent protein kinase kinase-β)-AMPK signaling pathway, thereby alleviating nonalcoholic hepatic steatosis …”