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Inhibition of O-GlcNAc transferase alleviates liver pathological changes in spontaneously obese mice

ZHANG Zi-Yang, LONG Xin-Yu, ZHANG Jia-Yi, LI Xiao-Shuang, KOU Le-Le, YANG Pei-Song, ZHANG Bo-Xi, XU Bin, LI Shi-Ze^*

Key Laboratory of Bovine Disease Control in Northeast China, Ministry of Agriculture and Rural Affairs, College of Animal Science and Veterinary Medicine, Heilongjiang Bayi Agricultural University, Daqing 163319, China

Abstract

This study was to explore the effects of O-GlcNAc transferase (OGT) inhibition on the liver pathological changes in spontaneously obese mice. Ten 6-week-old male ob/ob mice were randomly divided into a control group and a drug-treated group (receiving intraperitoneal injection of the OGT inhibitor OSMI-1). After 60 days of treatment, mouse liver tissue and serum samples were collected, and the expression levels of liver OGT and lipolysis-related proteins were detected by Western blot. Serum biochemical indexes were detected by full-automatic biochemical analyzer, and serum high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) were detected by corresponding kits. Liver pathological changes were detected by HE staining, oil red O staining, glycogen staining, and Masson staining. The results showed that compared with the control group, the body weight and liver mass of mice in the drug-treated group were significantly reduced. The levels of OGT protein expression and O-GlcNAc glycosylation modification in the liver were significantly down-regulated. The serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bile acid (TBA), lactate dehydrogenase (LDH), total cholesterol (TCHO), and triglycerides (TRIG) were significantly decreased. The levels of serum HDL-C and LDL-C were significantly reduced, and the expression levels of lipolysis-related proteins, including carnitine palmitoyltransferase 1A (CPT1A), CPT2, acyl-CoA oxidase 1 (ACOX1), and peroxisome proliferator-activated receptor α (PPARα) were significantly down-regulated. The number of hepatic lipid droplets was decreased significantly, the liver tissue had multiple nuclei and fewer vacuoles, the glycogen content was decreased significantly, and the collagen fiber content was increased significantly. These results suggest that OGT inhibition can improve abnormal serum indicators and accumulation of liver fat in spontaneously obese mice, thereby reducing liver pathological changes.

Key words: OSMI-1; O-GlcNAc glycosylation; liver; lipolysis

Received: 　　Accepted:

Corresponding author: 李士泽　　E-mail:

DOI: 10.13294/j.aps.2025.0095

Citing This Article：

ZHANG Zi-Yang, LONG Xin-Yu, ZHANG Jia-Yi, LI Xiao-Shuang, KOU Le-Le, YANG Pei-Song, ZHANG Bo-Xi, XU Bin, LI Shi-Ze. Inhibition of O-GlcNAc transferase alleviates liver pathological changes in spontaneously obese mice. Acta Physiol Sin 2025; 77 (6): 1201-1209 (in Chinese with English abstract).