Hinako Nakayama

Sarcopenia, characterized by skeletal muscle atrophy, was previously considered age-related; however, it is also associated with other diseases. Nonalcoholic fatty liver disease (NAFLD) is known to cause sarcopenia, and its complications have been reported to affect prognosis. The intestinal microbiota of patients with NAFLD or sarcopenia has been found to be altered compared to that of healthy individuals. However, the alterations that occur when both diseases coexist in humans or experimental animals remain unclear. Therefore, this study aimed to determine the intestinal microbiota changes associated with NAFLD with sarcopenia in SHRSP5/Dmcr rats at the time of concomitant disease. Fecal samples were collected from the rectum of SHRSP5/Dmcr rats fed a normal diet (non-NAFLD and non-Sarcopenia, n = 5) or a high-fat and high-cholesterol diet (NAFLD and Sarcopenia, n = 5) for 20 weeks, and subjected to 16S rRNA analysis. In the NAFLD and sarcopenia group, the diversity of the intestinal microbiota was reduced; further, the bacterial species reported in patients with NAFLD or sarcopenia were also changed. At the family level, the abundances of Akkermansiaceae, Bacteroidaceae, and Tannerellaceae were significantly higher whereas Ruminococcaceae and Lactobacillaceae were decreased in the NAFLD and sarcopenia group. At the genus level, the abundances of Akkermansia , Bacteroides , Ruminococcus , and Parabacteroides were significantly higher whereas the abundance of Lactobacillus was significantly decreased in the NAFLD and sarcopenia group. Overall, these findings help improve the existing understanding regarding the intestinal microbiota changes observed in conditions where NASH and sarcopenia co-occur.

The liver X receptor (LXR) can enhance cholesterol transporters, which could remove excess cholesterol from foam cells in atheromas. LXR has two subtypes: LXRα, which aggravates hepatic lipid accumulation, and LXRβ, which does not. In 2018, ouabagenin (OBG) was reported as a potential LXRβ-specific agonist. We aimed to examine whether OBG specifically affects LXRβ in nonalcoholic steatohepatitis (NASH); it did not aggravate hepatic steatosis and can suppress the development of atherosclerosis. SHRSP5/Dmcr rats fed a high-fat and high-cholesterol diet were divided into four groups as follows: (I) L-NAME group, (II) L-NAME/OBG group, (III) OBG (−) group, and (IV) OBG (+) group. All groups’ rats were intraperitoneally administered L-NAME. The L-NAME/OBG group’s rats were intraperitoneally administered OBG and L-NAME simultaneously. After L-NAME administration, the OBG (+) group’s rats were administered OBG, while the OBG (−) group’s rats were not. Although all rats developed NASH, OBG did not exacerbate steatosis (L-NAME/OBG and OBG (+) groups). In addition, endothelial cells were protected in the L-NAME/OBG group and foam cells in the atheroma were reduced in the OBG (+) group. OBG is an LXRβ-specific agonist and has a potential therapeutic effect on atherosclerosis without developing lipid accumulation in the liver.