Chronic fructose intake does not induce liver steatosis and inflammation in female Sprague-Dawley rats, but causes hypertriglyceridemia related to decreased VLDL receptor expression
Purpose: Sugar-sweetened beverage intake is a risk factor for insulin resistance, dyslipidemia, fatty liver, and steatohepatitis (NASH). Sub-chronic supplementation of liquid fructose, but not glucose, in female rats increases liver and plasma triglycerides without inflammation. We hypothesized that...
| Authors: | ; ; ; ; ; ; |
|---|---|
| Format: | Article |
| Status: | Accepted version |
| Publication date: | 2019 |
| Country: | España |
| Institution: | Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
| Repository: | Recercat. Dipósit de la Recerca de Catalunya |
| OAI Identifier: | oai:recercat.cat:2445/205843 |
| Online Access: | https://hdl.handle.net/2445/205843 |
| Access Level: | Open access |
| Keyword: | Fructosa Malalties del fetge Àcids grassos Fructose Liver diseases Fatty acids |
| _version_ | 1878729722582532096 |
|---|---|
| author | Sangüesa Puigventós, Gemma |
| author2 | Montañés, José Carlos Baena Muñoz, Miguel Sánchez, Rosa María Roglans i Ribas, Núria Alegret i Jordà, Marta Laguna Egea, Juan Carlos |
| author2_role | author author author author author author |
| author_browse | Alegret i Jordà, Marta Baena Muñoz, Miguel Laguna Egea, Juan Carlos Montañés, José Carlos Roglans i Ribas, Núria Sangüesa Puigventós, Gemma Sánchez, Rosa María |
| author_facet | Sangüesa Puigventós, Gemma Montañés, José Carlos Baena Muñoz, Miguel Sánchez, Rosa María Roglans i Ribas, Núria Alegret i Jordà, Marta Laguna Egea, Juan Carlos |
| author_role | author |
| collection | Recercat. Dipósit de la Recerca de Catalunya |
| description | Purpose: Sugar-sweetened beverage intake is a risk factor for insulin resistance, dyslipidemia, fatty liver, and steatohepatitis (NASH). Sub-chronic supplementation of liquid fructose, but not glucose, in female rats increases liver and plasma triglycerides without inflammation. We hypothesized that chronic supplementation of fructose would cause NASH and liver insulin resistance. Methods: We supplemented female Sprague-Dawley rats with water or either fructose or glucose 10% w/v solutions under isocaloric conditions for 7 months. At the end, plasma analytes, insulin, and adiponectin were determined, as well as liver triglyceride content and the expression of key genes controlling inflammation, fatty acid synthesis and oxidation, endoplasmic reticulum stress, and plasma VLDL clearance, by biochemical and histological methods. Results: Although sugar-supplemented rats increased their energy intake by 50-60%, we found no manifestation of liver steatosis, fibrosis or necrosis, unchanged plasma or tissue markers of inflammation or fibrosis, and reduced liver expression of gluconeogenic enzymes, despite both sugars increased fatty acid synthesis, mTORC1, and IRE1 activity, while decreasing fatty acid oxidation and PPARα activity. Only fructose-supplemented rats were hypertriglyceridemic, showing a reduced expression of VLDL receptor and lipoprotein lipase in skeletal muscle and vWAT. Glucose-supplemented rats showed increased adiponectinemia, which would explain the different metabolic outcomes of the two sugars. Conclusions: Chronic liquid simple sugar supplementation, as the sole risk factor, is not enough for female rats to develop NASH and increased liver gluconeogenesis. Nevertheless, under isocaloric conditions, only fructose induced hypertriglyceridemia, thus confirming that also the type of nutrient matters in the development of metabolic diseases. Keywords: Endoplasmic reticulum stress; Fatty acid metabolism; Glucose; NAFLD; UPR response. |
| eu_rights_str_mv | openAccess |
| format | article |
| id | ES_0dac35f97bc4e5c15cbdb93a3a2b0531 |
| institution | Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
| instname_str | Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
| network_acronym_str | ES |
| network_name_str | España |
| oai_identifier_str | oai:recercat.cat:2445/205843 |
| publishDate | 2019 |
| publishDateSort | 2019 |
| publisher | Springer Verlag |
| publisherStr | Springer Verlag |
| reponame_str | Recercat. Dipósit de la Recerca de Catalunya |
| spelling | Chronic fructose intake does not induce liver steatosis and inflammation in female Sprague-Dawley rats, but causes hypertriglyceridemia related to decreased VLDL receptor expression Sangüesa Puigventós, Gemma Montañés, José Carlos Baena Muñoz, Miguel Sánchez, Rosa María Roglans i Ribas, Núria Alegret i Jordà, Marta Laguna Egea, Juan Carlos Fructosa Malalties del fetge Àcids grassos Fructose Liver diseases Fatty acids Purpose: Sugar-sweetened beverage intake is a risk factor for insulin resistance, dyslipidemia, fatty liver, and steatohepatitis (NASH). Sub-chronic supplementation of liquid fructose, but not glucose, in female rats increases liver and plasma triglycerides without inflammation. We hypothesized that chronic supplementation of fructose would cause NASH and liver insulin resistance. Methods: We supplemented female Sprague-Dawley rats with water or either fructose or glucose 10% w/v solutions under isocaloric conditions for 7 months. At the end, plasma analytes, insulin, and adiponectin were determined, as well as liver triglyceride content and the expression of key genes controlling inflammation, fatty acid synthesis and oxidation, endoplasmic reticulum stress, and plasma VLDL clearance, by biochemical and histological methods. Results: Although sugar-supplemented rats increased their energy intake by 50-60%, we found no manifestation of liver steatosis, fibrosis or necrosis, unchanged plasma or tissue markers of inflammation or fibrosis, and reduced liver expression of gluconeogenic enzymes, despite both sugars increased fatty acid synthesis, mTORC1, and IRE1 activity, while decreasing fatty acid oxidation and PPARα activity. Only fructose-supplemented rats were hypertriglyceridemic, showing a reduced expression of VLDL receptor and lipoprotein lipase in skeletal muscle and vWAT. Glucose-supplemented rats showed increased adiponectinemia, which would explain the different metabolic outcomes of the two sugars. Conclusions: Chronic liquid simple sugar supplementation, as the sole risk factor, is not enough for female rats to develop NASH and increased liver gluconeogenesis. Nevertheless, under isocaloric conditions, only fructose induced hypertriglyceridemia, thus confirming that also the type of nutrient matters in the development of metabolic diseases. Keywords: Endoplasmic reticulum stress; Fatty acid metabolism; Glucose; NAFLD; UPR response. Springer Verlag https://hdl.handle.net/2445/205843 |
| spellingShingle | Chronic fructose intake does not induce liver steatosis and inflammation in female Sprague-Dawley rats, but causes hypertriglyceridemia related to decreased VLDL receptor expression Sangüesa Puigventós, Gemma Fructosa Malalties del fetge Àcids grassos Fructose Liver diseases Fatty acids |
| status_str | acceptedVersion |
| title | Chronic fructose intake does not induce liver steatosis and inflammation in female Sprague-Dawley rats, but causes hypertriglyceridemia related to decreased VLDL receptor expression |
| title_full | Chronic fructose intake does not induce liver steatosis and inflammation in female Sprague-Dawley rats, but causes hypertriglyceridemia related to decreased VLDL receptor expression |
| title_fullStr | Chronic fructose intake does not induce liver steatosis and inflammation in female Sprague-Dawley rats, but causes hypertriglyceridemia related to decreased VLDL receptor expression |
| title_full_unstemmed | Chronic fructose intake does not induce liver steatosis and inflammation in female Sprague-Dawley rats, but causes hypertriglyceridemia related to decreased VLDL receptor expression |
| title_short | Chronic fructose intake does not induce liver steatosis and inflammation in female Sprague-Dawley rats, but causes hypertriglyceridemia related to decreased VLDL receptor expression |
| title_sort | Chronic fructose intake does not induce liver steatosis and inflammation in female Sprague-Dawley rats, but causes hypertriglyceridemia related to decreased VLDL receptor expression |
| topic | Fructosa Malalties del fetge Àcids grassos Fructose Liver diseases Fatty acids |
| topic_facet | Fructosa Malalties del fetge Àcids grassos Fructose Liver diseases Fatty acids |
| url | https://hdl.handle.net/2445/205843 |