GPR40 agonist ameliorates liver X receptor-induced lipid accumulation in liver by activating AMPK pathway

Abstract

Hepatic steatosis is strongly linked to insulin resistance and type 2 diabetes. GPR40 is a G protein-coupled receptor mediating free fatty acid-induced insulin secretion and thus plays a beneficial role in the improvement of diabetes. However, the impact of GPR40 agonist on hepatic steatosis still remains to be elucidated. In the present study, we found that activation of GPR40 by its agonist GW9508 attenuated Liver X receptor (LXR)-induced hepatic lipid accumulation. Activation of LXR in the livers of C57BL/6 mice fed a high-cholesterol diet and in HepG2 cells stimulated by chemical agonist caused increased expression of its target lipogenic genes and subsequent lipid accumulation. All these effects of LXR were dramatically downregulated after GW9508 supplementation. Moreover, GPR40 activation was accompanied by upregulation of AMPK pathway, whereas the inhibitive effect of GPR40 on the lipogenic gene expression was largely abrogated by AMPK knockdown. Taken together, our results demonstrated that GW9508 exerts a beneficial effect to ameliorate LXR-induced hepatic steatosis through regulation of AMPK signaling pathway.

Systematically quantitative proteomics and metabolite profiles offer insight into fruit ripening behavior in Fragaria × ananassa

“…Strawberries from ve developmental stages were harvested and collected. Developmental stages were dened as small green (SG, seven days post-anthesis (DPA)), big green (BG, 14 DPA), white fruit (WF, 21 DPA), turning (TU, 28 DPA), and red fruit (RF, 35 DPA), as described by Li et al 21 The calyxes and pedicels of strawberry were removed and both strawberry achenes and receptacle were frozen in liquid nitrogen immediately before stored at À80 C. Three independent biological replications at three harvest times (Dec 5th 2015, Jan 5th 2016 and Feb 5th 2016) were prepared for each developmental stage using mixed achene and receptacle tissues from twenty ve individual strawberries for subsequent analyses.…”

“…[14][15][16][17][18][19] For strawberry, several research have been carried out to describe the proteomic changes in fruit ripening, 5,14 varietal difference, 20 strawberry allergen, 17 as well as response to environmental stress stimuli. 21,22 However, the relationship between the protein changes and the carbohydrate metabolism during strawberry ripening and development remains obscure.…”

Regulation of Hepatitis C Virus Infection by Cellular Retinoic Acid Binding Proteins through the Modulation of Lipid Droplet Abundance

“…In contrast, the expression of CRABP1 enhanced the activation of the LXR pathway. It is known that the activation of the FXR-RXR and PPAR-RXR pathways suppresses the accumulation of LDs, while the activation of the LXR-RXR pathway results in an increase in the abundance of LDs (15)(16)(17). Thus, the results from our bioinformatics analyses and the reporter assays collectively suggest that the expression of CRABP1 may result in the accumulation of LDs in hepatocytes.…”

Hesperetin inhibits foam cell formation in macrophages via activating LXRα signal in an AMPK dependent manner

“…However, there were several studies demonstrated that AMPK inhibited LXRα to prevent lipid accumulation in HepG2 cells (43,44). This discrepancy may be due to the different characteristic properties between pathological cell models, which suggests AMPK may have a selective regulation on LXRα in different pathological process.…”