PMID- 35715850 OWN - NLM STAT- MEDLINE DCOM- 20220621 LR - 20220729 IS - 1757-6512 (Electronic) IS - 1757-6512 (Linking) VI - 13 IP - 1 DP - 2022 Jun 17 TI - A long-term anti-inflammation markedly alleviated high-fat diet-induced obesity by repeated administrations of overexpressing IL10 human umbilical cord-derived mesenchymal stromal cells. PG - 259 LID - 10.1186/s13287-022-02935-8 [doi] LID - 259 AB - OBJECTIVES: Obesity is a chronic process and could activate various inflammatory responses, which in turn aggravates obesity and related metabolic syndrome. Here we explored whether long-term inhibition of inflammation could successfully alleviate high-fat diet (HFD)-induced obesity. METHODS: We constructed stable overexpressing interleukin 10 (IL10) human umbilical cord-derived mesenchymal stromal cells (HUCMSCs) which repeatedly were applied to obesity mice with HFD feeding to obtain a long-term anti-inflammation based on the prominent anti-inflammation effects of IL10 and immunomodulatery effects of HUCMSCs. Then we monitored the features of obesity including body weight, serum ALT, AST, and lipids. In addition, glucose homeostasis was determined by glucose tolerance and insulin sensitivity tests. The infiltrated macrophages in adipose tissues and hepatic lipid accumulation were detected, and the expressions of adipogenesis and inflammatory genes in adipose tissues were examined by real-time (RT) PCR and western blot analysis. RESULTS: Compared with HUCMSCs, IL10-HUCMSCs treatment had much better anti-obesity effects including body weight reduction, less hepatic lipids accumulation, lower amount and size of adipocyte, greater glucose tolerance, less systemic insulin resistance, and less adipose tissue inflammation in HFD feeding mice. Finally, IL10-HUCMSCs could decrease the activation of MAPK JNK of adipose tissue induced by HFD. The inhibition of MAPK JNK signal pathway by a small chemical molecule SP600125 in 3T3-L1 cells, a preadipocyte line, reduced the differentiation of adipocytes and lipid droplet accumulation. CONCLUSION: A lasting anti-inflammation based on gene modified stem cell therapy is an effective strategy in preventing diet-induced obesity and obesity-related metabolic syndrome. CI - (c) 2022. The Author(s). FAU - Wang, Liudi AU - Wang L AD - Clinical Stem Cell Center, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, 210000, China. FAU - Gao, Tianyun AU - Gao T AD - Clinical Stem Cell Center, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, 210000, China. FAU - Li, Yu AU - Li Y AD - State Key Laboratory of Pharmaceutical Biotechnology and the Comprehensive Cancer Center, School of Life Science, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing University, Nanjing, Jiangsu Province, China. FAU - Xie, Yuanyuan AU - Xie Y AD - Clinical Stem Cell Center, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, 210000, China. FAU - Zeng, Sheng AU - Zeng S AD - Clinical Stem Cell Center, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, 210000, China. FAU - Tai, Chenxu AU - Tai C AD - Clinical Stem Cell Center, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, 210000, China. FAU - Feng, Yirui AU - Feng Y AD - State Key Laboratory of Pharmaceutical Biotechnology and the Comprehensive Cancer Center, School of Life Science, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing University, Nanjing, Jiangsu Province, China. FAU - Shen, Pingping AU - Shen P AD - State Key Laboratory of Pharmaceutical Biotechnology and the Comprehensive Cancer Center, School of Life Science, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing University, Nanjing, Jiangsu Province, China. ppshen@nju.edu.cn. FAU - Wang, Bin AU - Wang B AUID- ORCID: 0000-0003-3981-8849 AD - Clinical Stem Cell Center, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, 210000, China. wangbin022800@126.com. AD - College of Life Sciences, Nanjing Normal University, Nanjing, 210023, China. wangbin022800@126.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20220617 PL - England TA - Stem Cell Res Ther JT - Stem cell research & therapy JID - 101527581 RN - 0 (IL10 protein, human) RN - 0 (Lipids) RN - 130068-27-8 (Interleukin-10) RN - IY9XDZ35W2 (Glucose) SB - IM MH - 3T3-L1 Cells MH - Adipose Tissue/metabolism MH - Animals MH - Body Weight MH - Diet, High-Fat/adverse effects MH - Glucose/metabolism MH - Humans MH - Inflammation/metabolism/therapy MH - *Insulin Resistance MH - Interleukin-10/genetics/metabolism MH - Lipids MH - *Mesenchymal Stem Cell Transplantation MH - *Mesenchymal Stem Cells/metabolism MH - *Metabolic Syndrome/metabolism MH - Mice MH - Mice, Inbred C57BL MH - Obesity/metabolism/therapy MH - Umbilical Cord PMC - PMC9204983 OTO - NOTNLM OT - Adipose tissue OT - Anti-inflammation OT - Gene modification OT - IL10 OT - MAPK OT - Obesity OT - Stem cell therapy OT - mesenchymal stromal cells (MSCs) COIS- The authors declare that they have no competing interests. EDAT- 2022/06/18 06:00 MHDA- 2022/06/22 06:00 PMCR- 2022/06/17 CRDT- 2022/06/17 23:45 PHST- 2022/01/14 00:00 [received] PHST- 2022/03/12 00:00 [accepted] PHST- 2022/06/17 23:45 [entrez] PHST- 2022/06/18 06:00 [pubmed] PHST- 2022/06/22 06:00 [medline] PHST- 2022/06/17 00:00 [pmc-release] AID - 10.1186/s13287-022-02935-8 [pii] AID - 2935 [pii] AID - 10.1186/s13287-022-02935-8 [doi] PST - epublish SO - Stem Cell Res Ther. 2022 Jun 17;13(1):259. doi: 10.1186/s13287-022-02935-8.