Sulfosuccinimidyl oleate ameliorates the high-fat diet-induced obesity syndrome by reducing intestinal and hepatic absorption

Qiming Ma; Li Wen; Yanxia Tian; Liqin Ma; Zhangsheng Wen; Yang Kun; Mengping Xu; Xiaoping Liu

doi:10.3389/fphar.2023.1193006

Sulfosuccinimidyl oleate ameliorates the high-fat diet-induced obesity syndrome by reducing intestinal and hepatic absorption

Front Pharmacol. 2023 May 26:14:1193006. doi: 10.3389/fphar.2023.1193006. eCollection 2023.

Authors

Qiming Ma¹, Li Wen², Yanxia Tian³, Liqin Ma⁴, Zhangsheng Wen⁵, Yang Kun³, Mengping Xu¹, Xiaoping Liu¹

Affiliations

¹ The Department of General Surgery, The First Affiliated Hospital of Gannan Medical University, Ganzhou, Jiangxi, China.
² Department of Neonatology, Ganzhou Maternal and Child Health Centre, Ganzhou, Jiangxi, China.
³ Department of Blood Transfusion, The First Affiliated Hospital of Gannan Medical University, Ganzhou, Jiangxi, China.
⁴ The Second Department of Surgery, People's Hospital of Shicheng County, Ganzhou, Jiangxi, China.
⁵ The CT Room of the Imaging Department, People's Hospital of Shicheng County, Ganzhou, Jiangxi, China.

Abstract

Background: A high-fat Western diet is a risk factor for obesity and steatosis. Reducing intestinal absorption of a high-fat diet (HFD) is a feasible strategy to control obesity. Sulfosuccinimidyl oleate (SSO) inhibits intestinal fatty acid transport. Therefore, the aim of this study was to investigate the effects of SSO on HFD-induced glucose and lipid metabolism in mice and its possible underlying mechanisms. Methods: Male C57/BL were fed a HFD (60% calories) for 12 weeks and were administered an oral dose of SSO (50 mg/kg/day). The expression of lipid absorption genes (CD36, MTTP, and DGAT1) and the serum levels of triglycerides (TGs), total cholesterol (TC), and free fatty acids (FFAs) were detected. Lipid distribution in the liver was detected by oil red and hematoxylin and eosin staining. In addition, serum levels of inflammatory factors, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) were measured to detect side effects. Results: SSO was effective in the treatment of obesity and metabolic syndrome induced by HFD in mice. It attenuated the assembly of intestinal epithelial chylomicrons by inhibiting intestinal epithelial transport and absorption of fatty acids, thereby reducing the gene expression levels of MTTP and DGAT1, resulting in decreased plasma TG and FFA levels. At the same time, it inhibited the transport of fatty acids in the liver and improved the steatosis induced by a HFD. The results of oil red staining showed that SSO treatment can reduce lipid accumulation in the liver by 70%, with no drug-induced liver injury detected on the basis of interleukin-6, C-reactive protein, ALT, and AST levels. In addition, SSO treatment significantly improved insulin resistance, decreased fasting blood glucose levels, and improved glucose tolerance in HFD-fed mice. Conclusion: SSO is effective in the treatment of obesity and metabolic syndrome induced by a HFD in mice. SSO reduces intestinal fatty acid absorption by reducing the inhibition of intestinal CD36 expression, followed by decreased TG and FFA levels, which attenuates HFD-induced fatty liver.

Keywords: high-fat diet; intestine; lipid absorption; obesity; sulfosuccinimidyl oleate.

Grants and funding

This study was supported by the key laboratory of colorectal and anorectal diseases in Ganzhou, Project Fund of Jiangxi Health Commission (202210908).