Licochalcone Suppresses LXRα-Induced Hepatic Lipogenic Gene Expression through AMPK/Sirt1 Pathway Activation

Abstract

Licochalcone (LC), a major phenolic retrochalcone from licorice, has anti-inflammatory activity. This study investigated the effects of licochalcone A (LCA) and licochalcone E (LCE) on Liver X receptor-α (LXRα)-mediated lipogenic gene expression and the molecular mechanisms underlying those effects. LCA and LCE antagonized the ability of LXRα agonists (T0901317 or GW3965) to increase sterol regulatory element binding protein-1c (SREBP-1c) expression and thereby inhibited target gene expression (e.g., FAS and ACC) in HepG2 cells. Moreover, treatment with LCA and LCE impaired LXRα/RXRα-induced CYP7A1-LXRE-luciferase (CYP7A1) transactivation. The AMPK-Sirt1 signaling pathway is an important regulator of energy metabolism and, therefore, a potential therapeutic target for metabolic diseases, including hepatic steatosis. We found here that LCE increased AMPK phosphorylation and Sirt1 expression. We conclude that LC inhibits SREBP-1c-mediated hepatic lipogenesis via activation of the AMPK/Sirt1 signaling pathway.

Amelioration of free fatty acid‐induced fatty liver by quercetin‐3‐O‐β‐D‐glucuronide through modulation of peroxisome proliferator‐activated receptor‐alpha/sterol regulatory element‐binding protein‐1c signaling

“…Our result exhibited that Q3GA dose‐dependently decreased SREBP‐1c and its downstream key gene FAS mRNA expression in in vitro and in vivo NAFLD models. In line with the present study, some flavonoids have given direct evidence that they downregulate SREBP‐1c involved in lipogenesis and ameliorating NAFLD disease . Surprisingly, we found that no change in mRNA expression of LXR‐α occurred compared with the model group.…”

Induction of Lipin1 by ROS-Dependent SREBP-2 Activation

“…After a two-step proteolytic cleavage, SREBPs are competent to transactivate genes involved in lipid synthesis (19,31). Sterol depletion and ethanol exposure have been reported to increase SREBP-dependent Lipin1 expression (32,33).…”

Inhibition of Adipocyte Differentiation by Anthocyanins Isolated from the Fruit ofVitis coignetiaePulliat is Associated with the Activation of AMPK Signaling Pathway

“…AMP-activated protein kinase (AMPK), which is recognized as a major regulator of fat metabolism, is a key sensory enzyme controlling energy metabolism ( 12 , 13 ). When AMPK is activated by phosphorylation by the upstream AMPK kinase, it functions as a cellular energy sensor through the regulation of fatty acid and glucose homeostasis ( 14 , 15 ). AMPK also induces inactivation by phosphorylating ACC, an important enzyme for fatty acid oxidation and biosynthesis ( 11 , 16 ).…”