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N-acetylcysteine (NAC) is an antioxidant, acting both directly and indirectly via upregulation of cellular antioxidants. We examined the mechanisms of liver steatosis after 12\u2009months high fat (HF) diet and tested the ability of NAC to rescue liver steatosis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Seven-week-old C57BL\/6 (B6) male mice were administered HF diet for 12\u2009months (HF group). Two other groups received HF diet for 12\u2009months accompanied by NAC for 12\u2009months (HFD\u2009+\u2009NAC(1\u201312)) or 6\u2009months (HFD\u2009+\u2009NAC(1\u20136)). The control group was fed regular diet for 12\u2009months (CD group).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Liver steatosis was more pronounced in the HF group than in the CD group after 12\u2009month feeding. NAC intake for 6 or 12\u2009months decreased liver steatosis in comparison with HF diet (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05). Furthermore, NAC treatment also reduced cellular apoptosis and caspase-3 expression. In the unfolded protein response (UPR) pathway, the expression of ECHS1, HSP60, and HSP70 was decreased in the HFD group (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05) and rescued by NAC therapy. With regards to the endoplasmic reticulum (ER) stress, Phospho-PERK (p-PERK) and ATF4 expression was decreased in the HF group, and only the HFD\u2009+\u2009NAC(1\u201312), but not HFD\u2009+\u2009NAC(1\u20136) group, showed significant improvement.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>HF diet for 12\u2009months induces significant liver steatosis via altered ER stress and UPR pathway activity, as well as liver apoptosis. NAC treatment rescues the liver steatosis and apoptosis induced by HF diet.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12944-020-01274-y","type":"journal-article","created":{"date-parts":[[2020,5,25]],"date-time":"2020-05-25T13:03:13Z","timestamp":1590411793000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":40,"title":["Long term N-acetylcysteine administration rescues liver steatosis via endoplasmic reticulum stress with unfolded protein response in mice"],"prefix":"10.1186","volume":"19","author":[{"given":"Ching-Chou","family":"Tsai","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Jen","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong-Ren","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li-Tung","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"You-Lin","family":"Tain","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I-Chun","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiunn-Ming","family":"Sheen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pei-Wen","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mao-Meng","family":"Tiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,5,25]]},"reference":[{"key":"1274_CR1","unstructured":"Obesity: preventing and managing the global epidemic. 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