PMID- 36501080 OWN - NLM STAT- MEDLINE DCOM- 20230105 LR - 20230105 IS - 2072-6643 (Electronic) IS - 2072-6643 (Linking) VI - 14 IP - 23 DP - 2022 Nov 27 TI - Ramulus Mori (Sangzhi) Alkaloids Ameliorate Obesity-Linked Adipose Tissue Metabolism and Inflammation in Mice. LID - 10.3390/nu14235050 [doi] LID - 5050 AB - Obesity has become a global epidemic disease as it is closely associated with a chronic low-grade inflammatory state that results in metabolic dysfunction. Ramulus Mori (Sangzhi) alkaloids (SZ-A) derived from Morus alba L. were licensed to treat type 2 diabetes (T2DM) in 2020. In this study, we explored the effect of SZ-A on adipose tissue metabolism and inflammation using an obesity model induced by a high-fat diet (HFD). C57BL/6J mice were fed high fat for 14 weeks and followed by SZ-A 400 mg/kg treatment via gavage for another six weeks, during which they were still given the high-fat diet. The results showed that SZ-A notably reduced body weight and serum levels of lipid metabolism-related factors, such as triglycerides (TG) and total cholesterol (TC); and inflammation-related factors, namely tumor necrosis factor alpha (TNFalpha), interleukin 6 (IL6), fibrinogen activator inhibitor-1 (PAI-1), angiopoietin-2 (Ang-2), and leptin (LEP), in the HFD-induced mice. SZ-A increased the protein and mRNA expression of lipid metabolism-related factors, including phosphorylated acetyl coenzyme A carboxylase (p-ACC), phosphorylated hormone-sensitive triglyceride lipase (p-HSL), adipose triglyceride lipase (ATGL), and peroxisome proliferator-activated receptor-alpha (PPARalpha), in adipose tissue. Immunohistochemistry results demonstrated that SZ-A significantly reduced the infiltration of pro-inflammatory M1-type macrophages in epididymal fat. The data also suggested that SZ-A down-regulates the transcriptional levels of inflammatory factors Il6, Tnfalpha, monocyte chemoattractant protein-1 (Mcp1), and F4/80, and up-regulates interleukin 4 (Il4), interleukin 10 (Il10), and interleukin 13 (Il13) in adipose tissue. Overall, the results indicate that SZ-A exhibits potential in regulating lipid metabolism and ameliorating obesity-linked adipose inflammation. FAU - Sun, Qian-Wen AU - Sun QW AD - State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China. AD - Beijing Key Laboratory of Drug Delivery Technology and Novel Formulation, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China. FAU - Lian, Chun-Fang AU - Lian CF AUID- ORCID: 0000-0003-0658-0635 AD - State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China. AD - Beijing Key Laboratory of Drug Delivery Technology and Novel Formulation, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China. FAU - Chen, Yan-Min AU - Chen YM AD - State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China. AD - Beijing Key Laboratory of Drug Delivery Technology and Novel Formulation, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China. FAU - Ye, Jun AU - Ye J AD - State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China. AD - Beijing Key Laboratory of Drug Delivery Technology and Novel Formulation, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China. FAU - Chen, Wei AU - Chen W AD - State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China. AD - Beijing Key Laboratory of Drug Delivery Technology and Novel Formulation, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China. FAU - Gao, Yue AU - Gao Y AD - State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China. AD - Beijing Key Laboratory of Drug Delivery Technology and Novel Formulation, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China. FAU - Wang, Hong-Liang AU - Wang HL AUID- ORCID: 0000-0002-5905-3225 AD - State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China. AD - Beijing Key Laboratory of Drug Delivery Technology and Novel Formulation, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China. FAU - Gao, Li-Li AU - Gao LL AD - State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China. AD - Beijing Key Laboratory of Drug Delivery Technology and Novel Formulation, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China. FAU - Liu, Yu-Ling AU - Liu YL AD - State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China. AD - Beijing Key Laboratory of Drug Delivery Technology and Novel Formulation, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China. FAU - Yang, Yan-Fang AU - Yang YF AD - State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China. AD - Beijing Key Laboratory of Drug Delivery Technology and Novel Formulation, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China. LA - eng GR - 2021-I2M-1-028 & 2022-I2M-JB-011 & 2021-I2M-1-026/CAMS Innovation Fund for Medical Sciences (CIFMS)/ GR - 2018ZX09711001 & 2018ZX09721003/National Science and Technology Major Project/ PT - Journal Article DEP - 20221127 PL - Switzerland TA - Nutrients JT - Nutrients JID - 101521595 RN - EC 3.1.1.3 (Lipase) RN - Morus alba SB - IM MH - Animals MH - Mice MH - Adipose Tissue/metabolism MH - *Diabetes Mellitus, Type 2/metabolism MH - Diet, High-Fat MH - Inflammation/metabolism MH - Lipase/metabolism MH - Lipid Metabolism MH - Mice, Inbred C57BL MH - Obesity/metabolism PMC - PMC9739644 OTO - NOTNLM OT - Ramulus Mori alkaloids OT - adipose inflammation OT - adipose tissue OT - lipid metabolism OT - obesity COIS- The authors declare no conflict of interest. EDAT- 2022/12/12 06:00 MHDA- 2022/12/15 06:00 PMCR- 2022/11/27 CRDT- 2022/12/11 01:31 PHST- 2022/10/07 00:00 [received] PHST- 2022/11/21 00:00 [revised] PHST- 2022/11/24 00:00 [accepted] PHST- 2022/12/11 01:31 [entrez] PHST- 2022/12/12 06:00 [pubmed] PHST- 2022/12/15 06:00 [medline] PHST- 2022/11/27 00:00 [pmc-release] AID - nu14235050 [pii] AID - nutrients-14-05050 [pii] AID - 10.3390/nu14235050 [doi] PST - epublish SO - Nutrients. 2022 Nov 27;14(23):5050. doi: 10.3390/nu14235050.