We provided evidences that changes in the gut microbiota and their metabolites can alter the profile of BAs, thereby providing a mechanism by which an altered microbiota profile contributes to the development of NAFLD.

Germinated brown rice (GBR, Orysa sartiva L.) has been reported to have anti‐obesity and anti‐inflammatory effects. However, the mechanisms underlying the anti‐inflammatory effect of GBR on adipocytes are not fully understood. The aim of this study was to explore the anti‐inflammatory mechanisms of GBR on lipopolysaccharide (LPS)‐stimulated 3T3‐L1 adipocytes. 3T3‐L1 adipocytes were pretreated with GBR extracts (0–20 mg/ml) 1h before LPS stimulation. The mRNA expressions of adipokines and Toll‐like receptor 4 (TLR4) were measured by RT‐PCR. The protein expressions of TLR4‐related molecules were detected by western blotting and nuclear factor‐κB (NF‐κB) activation was measured. Our results showed that GBR extract dose‐dependently inhibited mRNA expressions of LPS‐induced tumor necrosis factor‐α (TNF‐α), interleukin‐6 (IL‐6), and monocyte chemoattractant protein‐1 (MCP‐1). GBR extract was found to inhibit LPS‐induced mRNA expression of TLR4 and protein expressions of both myeloid differentiation factor 88 (MyD88) and TNF receptor‐associated factor 6 (TRAF6). Furthermore, GBR extract significantly inhibited extracellular receptor‐activated kinase (ERK) phosphorylation and NF‐κB activation. These results suggest that GBR extract has the anti‐inflammatory property on LPS‐induced inflammation via inhibiting TLR4 signaling including ERK and NF‐κB signaling pathways in adipocytes. (This research was supported by the Soonchunhyang University Research Fund.)This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Estrogen deficiency is associated with obesity, dyslipidemia, and increased insulin resistance in postmenopausal women. Development of an efficient therapeutic agent without side effects is needed to prevent or improve postmenopausal symptoms and diseases induced by estrogen deficiency. This study was performed to investigate the effects of water extract from Agrimonia pilosa Ledeb. on glucose and lipid metabolism in ovariectomized rats fed high fat diet. Female Sprague Dawley rats were sham operated or ovariectomized and after 3 weeks, assigned to the following groups: sham‐operated + high fat diet(S); ovariectomized + high fat diet (OVX); ovariectomized + high fat diet with 0.1% A. pilosa water extract (OVX+0.1A); ovariectomized + high fat diet with 0.5% A. pilosa water extract (OVX+0.5A). In our results, ovariectomy significantly increased body weight and dietary intake compare with sham group (p<0.05), however there was no significant difference in weight gain and dietary intake by A. pilosa treatment. Blood triglyceride, total‐cholesterol, and LDL‐cholesterol showed a tendency to decrease in A. pilosa supplemented groups. In glucose metabolism, we observed the blood glucose levels of the OVX+0.1A and OVX+0.5A groups were lower than those of the OVX group (p<0.05). Blood adiponectin concentration was also increased significantly by A. pilosa treatment in ovariectomized group (p<0.05). Additionally, we investigated the suppressive effect of A. pilosa aqueous extract on hepatic lipid accumulation. These effects were accompanied by reduced hepatic tissue expression of steatosis‐related genes. These data suggest that A. pilosa improves glucose tolerance and hepatic steatosis in ovariectomized rats.Support or Funding InformationThis study was supported by a research project of the National Institute of Agricultural Science of the Rural Development Administration, Republic of Korea (project no. PJ008554), and by the National Research Foundation of Korea(NRF) grant funded by the Korea government(MSIT) (No. 2017R1C1B5018328).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Recent studies have showed that diet‐induced alterations of gut microbiota composition play a pivotal role in the development of metabolic diseases. We investigated whether dietary fat and age would affect gut microbiota, permeability and inflammation. C57BL/6J mice were randomly assigned to either normal fat diet (ND) or high‐fat diet (HD) group. After 10 wks, a half of mice in each group were switched to either HD or ND feeding for additional 10 wks. Microbiome composition and diversity were analyzed by 16S rRNA‐based pyrosequencing. Colonic mRNA expressions of tight junction (TJ) proteins and inflammatory cytokines were measured by qPCR. DNA strand break was determined using comet assay. The main bacterial phyla of mice were Frimicutes, Bacteroidetes, and Actinobacteria. Diversity of gut microbiota was reduced in mice fed HD compared to those of mice fed ND. In mice fed HD for 20 wks, the proportions of Actinobacteria and Firmicutes increased while the proportion of Bacteroidetes decreased compared to mice fed ND for 20wks. The proportions of Firmicutes and Bacteroidetes were related with age while the proportion of Actinobacteria was related with dietary fat content. High‐fat diet was negatively associated with the expressions of TJ proteins while it was positively associated with the expression of inflammatory cytokines. Changes in the expression of TJ protein and inflammatory cytokines followed changes in fat content of the diet. Our data showed that both dietary fat intake and age affect gut microbiota composition as well as colonic membrane integrity and inflammation. [This study was supported by the Mid‐Career Research Program 2012R1A2A2A01046228 NRF]