Sulfosuccinimidyl oleate ameliorates the high-fat diet-induced obesity syndrome by reducing intestinal and hepatic absorption
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 investig...
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Frontiers Media S.A.
2023-05-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2023.1193006/full |
| _version_ | 1827940928720994304 |
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| author | Qiming Ma Li Wen Yanxia Tian Liqin Ma Zhangsheng Wen Yang Kun Mengping Xu Xiaoping Liu |
| author_facet | Qiming Ma Li Wen Yanxia Tian Liqin Ma Zhangsheng Wen Yang Kun Mengping Xu Xiaoping Liu |
| author_sort | Qiming Ma |
| collection | DOAJ |
| description | 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. |
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| language | English |
| last_indexed | 2024-03-13T09:28:33Z |
| publishDate | 2023-05-01 |
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| spelling | doaj.art-c0c99753a9314a6baf1f18be6cabcb9b2023-05-26T04:38:59ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122023-05-011410.3389/fphar.2023.11930061193006Sulfosuccinimidyl oleate ameliorates the high-fat diet-induced obesity syndrome by reducing intestinal and hepatic absorptionQiming Ma0Li Wen1Yanxia Tian2Liqin Ma3Zhangsheng Wen4Yang Kun5Mengping Xu6Xiaoping Liu7The Department of General Surgery, The First Affiliated Hospital of Gannan Medical University, Ganzhou, Jiangxi, ChinaDepartment of Neonatology, Ganzhou Maternal and Child Health Centre, Ganzhou, Jiangxi, ChinaDepartment of Blood Transfusion, The First Affiliated Hospital of Gannan Medical University, Ganzhou, Jiangxi, ChinaThe Second Department of Surgery, People’s Hospital of Shicheng County, Ganzhou, Jiangxi, ChinaThe CT Room of the Imaging Department, People’s Hospital of Shicheng County, Ganzhou, Jiangxi, ChinaDepartment of Blood Transfusion, The First Affiliated Hospital of Gannan Medical University, Ganzhou, Jiangxi, ChinaThe Department of General Surgery, The First Affiliated Hospital of Gannan Medical University, Ganzhou, Jiangxi, ChinaThe Department of General Surgery, The First Affiliated Hospital of Gannan Medical University, Ganzhou, Jiangxi, ChinaBackground: 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.https://www.frontiersin.org/articles/10.3389/fphar.2023.1193006/fullintestineobesitylipid absorptionsulfosuccinimidyl oleatehigh-fat diet |
| spellingShingle | Qiming Ma Li Wen Yanxia Tian Liqin Ma Zhangsheng Wen Yang Kun Mengping Xu Xiaoping Liu Sulfosuccinimidyl oleate ameliorates the high-fat diet-induced obesity syndrome by reducing intestinal and hepatic absorption Frontiers in Pharmacology intestine obesity lipid absorption sulfosuccinimidyl oleate high-fat diet |
| title | Sulfosuccinimidyl oleate ameliorates the high-fat diet-induced obesity syndrome by reducing intestinal and hepatic absorption |
| title_full | Sulfosuccinimidyl oleate ameliorates the high-fat diet-induced obesity syndrome by reducing intestinal and hepatic absorption |
| title_fullStr | Sulfosuccinimidyl oleate ameliorates the high-fat diet-induced obesity syndrome by reducing intestinal and hepatic absorption |
| title_full_unstemmed | Sulfosuccinimidyl oleate ameliorates the high-fat diet-induced obesity syndrome by reducing intestinal and hepatic absorption |
| title_short | Sulfosuccinimidyl oleate ameliorates the high-fat diet-induced obesity syndrome by reducing intestinal and hepatic absorption |
| title_sort | sulfosuccinimidyl oleate ameliorates the high fat diet induced obesity syndrome by reducing intestinal and hepatic absorption |
| topic | intestine obesity lipid absorption sulfosuccinimidyl oleate high-fat diet |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2023.1193006/full |
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