title: Stem cell transplantation upregulates Sirt1 and antioxidant expression, ameliorating fatty liver in type 2 diabetic mice.
abstract: Nonalcoholic fatty liver disease (NAFLD) is associated with insulin resistance, oxidative stress, and obesity. The db/db mouse model displays increased levels of insulin resistance, obesity, and an over-accumulation of hepatic triglycerides, making it an excellent model for studying NAFLD. In db/db mice, intra-bone marrow-bone marrow transplantation plus thymus transplantation (IBM-BMT+TT) improves type 2 diabetes mellitus (T2 DM) by normalizing the T-cell imbalance. We hypothesized that this approach would improve Sirt1 expression in the liver and benefit liver development. The db/db mice were treated with IBM-BMT+TT, and plasma MCP-1, IL-6, adiponection, LDL, Sirt1, and HO-1 levels were then assessed. Stem cell transplantation decreased the levels of plasma inflammatory cytokines and LDL while it increased the expression of Sirt1 and HO-1, resulting in decreased progression of fatty liver. Moreover, Sirt1 and HO-1 expression were both detected in the thymus and many HO-1-positive cells were observed in the bone marrow. This is the first report of stem cell transplantation improving the antioxidant function in the liver, thymus, and bone marrow of db/db mice by increasing the levels of Sirt1 and HO-1. This approach may prove useful in the treatment of nonalcoholic steatohepatitis and its clinical manifestations.
authors: 1. Department of Stem Cell Disorders, Kansai Medical University, Hirakata City, Osaka, Japan.
authors: Ming
authors: M
authors: Li
authors: 2. Department of Cardiac Surgery, Beijing Institute of Heart, Lung and Blood Vessel Disease, Beijing Anzhen Hospital Affiliated to Capital Medical University, Beijing, China.
authors: Kequan
authors: K
authors: Guo
authors: 3. Department of Drug Science, Section of Biochemistry, University of Catania, Catania, Italy.
authors: Luca
authors: L
authors: Vanella
authors: 4. Department of Biotechnology, Kyoto Institute of Technology, Kyoto, Japan.
authors: Shigeru
authors: S
authors: Taketani
authors: 5. Division of Surgical Pathology, Toyooka Hospital, Hyogo, Japan.
authors: Yasushi
authors: Y
authors: Adachi
authors: 1. Department of Stem Cell Disorders, Kansai Medical University, Hirakata City, Osaka, Japan.
authors: Susumu
authors: S
authors: Ikehara
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D015153:Blotting, Western; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000628:therapy; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism* / Q000628:therapy*; D005234:Fatty Liver / Q000378:metabolism* / Q000628:therapy*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D056564:Sirtuin 1 / Q000235:genetics / Q000378:metabolism*; D033581:Stem Cell Transplantation
chemical_list: D000975:Antioxidants; C470545:Sirt1 protein, mouse; D056564:Sirtuin 1
keywords: HO-1; Sirt1; nonalcoholic fatty liver disease; obesity.; stem cell transplantation