Protective effect of SGL5213, a potent intestinal sodium–glucose cotransporter 1 inhibitor, in nonalcoholic fatty liver disease in mice

• Published in: Journal of pharmacological sciences 2021-10, Vol.147 (2), p.176-183
• Main Authors: Honda, Yasushi, Ozaki, Anna, Iwaki, Michihiro, Kobayashi, Takashi, Nogami, Asako, Kessoku, Takaomi, Ogawa, Yuji, Tomeno, Wataru, Imajo, Kento, Yoneda, Masato, Saito, Satoru, Nagashima, Yoji, Nakajima, Atsushi
• Format: Article
• Language: English
• Subjects: 1-Deoxynojirimycin - administration & dosage; 1-Deoxynojirimycin - analogs & derivatives; Animals; Chronic Disease; Diet, High-Fat - adverse effects; Dietary Sucrose - adverse effects; Disease Models, Animal; Gastrointestinal Absorption - drug effects; Gene Expression - drug effects; Glucose - metabolism; Insulin Resistance; Male; Mice; Mice, Inbred C57BL; Miglitol; NAFLD; NASH; Non-alcoholic Fatty Liver Disease - drug therapy; Non-alcoholic Fatty Liver Disease - etiology; Non-alcoholic Fatty Liver Disease - metabolism; Non-alcoholic Fatty Liver Disease - prevention & control; Obesity - drug therapy; Patient Acuity; RNA, Messenger - genetics; RNA, Messenger - metabolism; SGL5213; SGLT1 inhibitor; Sodium-Glucose Transporter 1 - antagonists & inhibitors; Sodium-Glucose Transporter 1 - genetics; Sodium-Glucose Transporter 1 - metabolism; Sorbitol - administration & dosage; Sorbitol - analogs & derivatives; Sorbitol - pharmacology
• ISSN: 1347-8613; 1347-8648
• DOI: 10.1016/j.jphs.2021.07.002

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic disease. SGL5213, which is minimally absorbed and is restricted to the intestinal tract, is a potent intestinal sodium–glucose cotransporter 1 (SGLT1) inhibitor. In this study, we investigated the protective effect of SGL5213 in a rodent model of NAFLD. Using a rodent model of NAFLD, we compared SGL5213 efficacy with miglitol, which is an α-glucosidase inhibitor. We used a high-fat and high-sucrose diet-induced NAFLD model. SGL5213 and miglitol improved obesity, liver dysfunction, insulin resistance, and the NAFLD severity. To further investigate the effects of SGL5213, we analyzed the mRNA expression of genes involved in lipid metabolism, inflammation, and liver fibrosis, and cecal pH levels. SGL5213 and miglitol treatment significantly decreased mRNA expression of factors involved in inflammation and liver fibrosis. SGL5213 treatment significantly decreased cecal pH levels, which did not occur with miglitol. SGL5213 had a protective effect on the pathogenesis of NAFLD in a rodent model. We considered that inhibiting glucose absorption and increasing glucose content in the gastrointestinal tract with SGL5213 might have contributed to the protective effect in NAFLD. SGL5213 is a promising therapeutic agent for NAFLD with obesity and insulin resistance.