Macrophage specific restoration of the Nrf2 gene in whole-body knockout mice ameliorates steatohepatitis induced by lipopolysaccharide from Porphyromonas gingivalis through enhanced hepatic clearance.

Lipopolysaccharide (LPS) derived from Porphyromonas gingivalis (P.g.), which causes periodontal disease, contributes to the development of non-alcoholic steatohepatitis (NASH). We investigated the role of Nrf2, an antioxidative stress sensor, in macrophages in the development of NASH induced by LPS from P.g. We generated macrophage-specific Nrf2 gene rescue mice (Nrf2-mRes), which express Nrf2 only in macrophages, using the cre/loxp system. Wild-type (WT) mice, whole body Nrf2-knockout (Nrf2-KO) mice, and Nrf2-mRes mice were fed a high-fat diet for 18 weeks, and LPS from P.g. was administered intraperitoneally for the last 6 weeks. Nrf2-KO mice developed severe steatohepatitis with liver inflammation and fibrosis compared with WT mice, and steatohepatitis was ameliorated in Nrf2-mRes mice. The mRNA expressions of Toll-like receptor (Tlr)-2, which activates inflammatory signaling pathways after LPS binding, and α-smooth muscle actin (αSma), which promotes hepatic fibrosis, were reduced in Nrf2-mRes mice compared with Nrf2-KO mice. The protein levels of LPS-binding protein in livers were increased in Nrf2-KO mice compared with WT mice; however, the levels were reduced in Nrf2-mRes mice despite similar numbers of F4/80 positive cells, which reflect macrophage/Kupffer cell infiltration into the livers. Nrf2 in macrophages ameliorates NASH through the increased hepatic clearance of LPS.

Survey of Dietary Habits and Physical Activity in Japanese Patients with Non-Obese Non-Alcoholic Fatty Liver Disease.

The incidence of non-obese non-alcoholic fatty liver disease (NAFLD), characterized by the presence of a fatty liver in individuals with a normal body mass index, is on the rise globally. Effective management strategies, including lifestyle interventions such as diet and exercise therapy, are urgently needed to address this growing public health concern. The aim of this study was to investigate the association between non-obese NAFLD, dietary habits, and physical activity levels. By elucidating these relationships, this research may contribute to the development of evidence-based recommendations for the management of non-obese NAFLD. The study had a single-center retrospective cross-sectional design and compared clinical data and dietary and physical activity habits between patients with and without non-obese NAFLD. Logistic regression analysis was utilized to investigate the relationship between food intake frequency and the development of NAFLD. Among the 455 patients who visited the clinic during the study period, 169 were selected for analysis, including 74 with non-obese NAFLD and 95 without NAFLD. The non-obese NAFLD group showed a less-frequent consumption of fish and fish products as well as olive oil and canola/rapeseed oil, while they showed more frequent consumption of pastries and cake, snack foods and fried sweets, candy and caramels, salty foods, and pickles compared to the non-NAFLD group. Logistic regression analysis revealed that NAFLD was significantly associated with the consumption of fish, fish products, and pickles at least four times a week. The physical activity level was lower and the exercise frequency was lower in patients with non-obese NAFLD compared to those without NAFLD. The results of this study suggest that a low consumption of fish and fish products and high consumption of pickles may be associated with a higher risk of non-obese NAFLD. Moreover, dietary habits and physical activity status should be taken into consideration for the management of patients with non-obese NAFLD. It is important to develop effective management strategies, such as dietary and exercise interventions, to prevent and treat NAFLD in this patient population.