Description: Hyperhomocysteinemia (HHcy) is associated with liver diseases such as fatty liver and hepatic fibrosis; however, the underlying mechanism is still largely unknown. The current study aimed to explore the signaling pathway involved in HHcy-induced hepatic steatosis. C57BL/6 mice were fed a high-methionine diet (HMD) for 4 and 8 weeks to establish the HHcy mouse model. Compared to a chow diet, the HMD induced hepatic steatosis and elevated hepatic expression of CD36, a fatty acid transport protein. The increased CD36 expression was associated with activation of the aryl hydrocarbon receptor (AHR). In primary cultured hepatocytes, high levels of homocysteine (Hcy) treatment upregulated CD36 and increased subsequent lipid uptake; both were significantly attenuated by siRNA knockdown of CD36 and AHR. Chromatin immunoprecipitation assay revealed that Hcy promoted the binding of AHR to the CD36 promoter, and transient transfection assay demonstrated markedly increased activity of the AHR response element by Hcy, which was ligand-dependent. Mass spectrometry revealed significantly increased hepatic content of lipoxin A 4 (LXA 4 ), a metabolite of arachidonic acid, in HMD-fed mice. Further, over-expression of 15-oxoprostaglandin 13-reductase 1, a LXA 4 inactivation enzyme, inhibited Hcy-induced AHR activation, lipid uptake and lipid accumulation. Moreover, LXA 4 -induced upregulation of CD36 and lipid uptake was inhibited by AHR siRNA in vitro in hepatocytes. Finally, treatment with an AHR antagonist reversed the HHcy-induced lipid accumulation by inhibiting the AHR-CD36 pathway in mice. In conclusion, our results strongly suggest that HHcy activated the AHR-CD36 pathway by increasing hepatic LXA 4 content, which resulted in hepatic steatosis. This article is protected by copyright. All rights reserved.

Description: Similar to loess-paleosol sequences in northwestern China, terrestrial sedimentary sequences (red soils) in southern China also provide sensitive Quaternary records of subtropical/tropical paleoclimate and paleoenvironment. Compared with red clay sequences originated from eolian dust, red soils derived from bedrock have received little attention. In this study, a long core of red soil derived from weathered basalt in northern Hainan Island, China, was systematically investigated using detailed magnetic measurements and rare earth element analyses. The results show that an extremely strong magnetic zone with a maximum magnetic susceptibility (〉10 × 10 –5 m 3 kg –1 ) is interbedded in the middle of the core profile. This layer contains a significant amount of superparamagnetic magnetite/maghemite particles that primarily originated from volcanic ash, with secondary contributions from pedogenesis. The former has an average grain size of ~19 nm with a normal distribution of volume, and the latter has a much wider grain size distribution. The presence of volcanic ash within the red soil indicates that these Quaternary basalts were not formed by continuous volcanic eruptions. Moreover, the magnetic enhancement patterns differ between the upper and lower zones. The upper zone is more magnetically enhanced and experienced higher precipitation and temperature than the lower zone. Discrimination of superparamagnetic particles originating from pedogenic processes and volcanic ash thus provides a sound theoretical base for accurate interpretation of magnetism in red soils in this region.