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This study was designed to assess the effectiveness of grape seed and skin extract (GSSE) and orlistat (Xenical, Xe) on high-fat diet (HFD)-induced spleen lipotoxicity. Obese rats were treated either with GSSE (4 g\/kg body weight) or Xe (2 mg\/kg body weight) or GSSE+Xe and monitored for weight loss for 3 months. Animals were then sacrificed and their spleen used for the evaluation of lipotoxicity-induced oxidative stress and inflammation as well as the putative protection afforded by GSSE and Xe treatment. HFD induced body weight gain and glycogen accumulation into the spleen; ectopic deposition of cholesterol and triglycerides and an oxidative stress characterized by increased lipoperoxidation and carbonylation; inhibition of antioxidant enzyme activities, such as catalase, glutathione peroxidase, and superoxide dismutase; depletion of zinc and copper; and a concomitant increase in calcium. HFD also increased plasma pro-inflammatory cytokines, such as interleukin (IL)-6, IL-17A, tumour necrosis factor alpha, and C-reactive protein, and decreased plasma IL-10 and adiponectin. Importantly, GSSE counteracted all the deleterious effects of HFD on spleen (i.e., lipotoxicity, oxidative stress, and inflammation) and the best protection was obtained when combining Xe+GSSE. Combining GSSE with Xe prevented against fat-induced spleen lipotoxicity, oxidative stress, and inflammation; this combination may be beneficial in other diseases related to the spleen. <\/jats:p>","DOI":"10.1139\/apnm-2017-0743","type":"journal-article","created":{"date-parts":[[2018,3,7]],"date-time":"2018-03-07T22:36:22Z","timestamp":1520462182000},"page":"782-794","update-policy":"https:\/\/doi.org\/10.1139\/csp-crossmark-policy","source":"Crossref","is-referenced-by-count":14,"title":["Supplementation of grape seed and skin extract to orlistat therapy prevents high-fat diet-induced murine spleen lipotoxicity"],"prefix":"10.1139","volume":"43","author":[{"given":"Takwa","family":"Bedhiafi","sequence":"first","affiliation":[{"name":"Faculty of Sciences of Bizerte, University of Carthage, 7021 Jarzouna, Tunisia."},{"name":"Laboratory of Bioactive Substances, Center of Biotechnology of Borj Cedria, BP 901, 2050 Hammam Lif, Tunisia."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kamel","family":"Charradi","sequence":"additional","affiliation":[{"name":"Faculty of Sciences of Bizerte, University of Carthage, 7021 Jarzouna, Tunisia."},{"name":"Laboratory of Bioactive Substances, Center of Biotechnology of Borj Cedria, BP 901, 2050 Hammam Lif, Tunisia."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mouna Ben","family":"Azaiz","sequence":"additional","affiliation":[{"name":"Immunology Department, Military Hospital of Tunis, Tunis, 1008, Tunisia."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohamed","family":"Mahmoudi","sequence":"additional","affiliation":[{"name":"Faculty of Sciences of Bizerte, University of Carthage, 7021 Jarzouna, Tunisia."},{"name":"Laboratory of Bioactive Substances, Center of Biotechnology of Borj Cedria, BP 901, 2050 Hammam Lif, Tunisia."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Issam","family":"Msakni","sequence":"additional","affiliation":[{"name":"Anatomy and Cyto-Pathology Department, Military Hospital, Mont-Fleury, Tunis, 1008, Tunisia."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Khawla","family":"Jebari","sequence":"additional","affiliation":[{"name":"Faculty of Sciences of Bizerte, University of Carthage, 7021 Jarzouna, Tunisia."},{"name":"Laboratory of Bioactive Substances, Center of Biotechnology of Borj Cedria, BP 901, 2050 Hammam Lif, Tunisia."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ammar","family":"Bouziani","sequence":"additional","affiliation":[{"name":"Anatomy and Cyto-Pathology Department, Military Hospital, Mont-Fleury, Tunis, 1008, Tunisia."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ferid","family":"Limam","sequence":"additional","affiliation":[{"name":"Laboratory of Bioactive Substances, Center of Biotechnology of Borj Cedria, BP 901, 2050 Hammam Lif, Tunisia."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ezzedine","family":"Aouani","sequence":"additional","affiliation":[{"name":"Faculty of Sciences of Bizerte, University of Carthage, 7021 Jarzouna, Tunisia."},{"name":"Laboratory of Bioactive Substances, Center of Biotechnology of Borj Cedria, BP 901, 2050 Hammam Lif, Tunisia."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"155","reference":[{"key":"refg1\/ref1","unstructured":"Aebi, H. 1974. 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