PMID- 38003291 OWN - NLM STAT- MEDLINE DCOM- 20231129 LR - 20231129 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 24 IP - 22 DP - 2023 Nov 8 TI - Dipeptidyl Peptidase 4 Stimulation Induces Adipogenesis-Related Gene Expression of Adipose Stromal Cells. LID - 10.3390/ijms242216101 [doi] LID - 16101 AB - Adipogenesis has emerged as a new therapeutic target for regulating metabolism and achieving anti-inflammatory and anti-atherosclerotic effects via the release of adiponectin. However, at present, the effects and mechanism of action of dipeptidyl peptidase 4 (DPP4) stimulation on adiponectin production and adipogenesis have not been clarified. Here, we investigated the effects of DPP4 stimulation with monocyte chemoattractant protein-1 (MCP-1) on platelet-derived growth factor receptor alpha (PDGFRalpha) expression in adipose tissue and blood adiponectin levels. Stromal vascular fractions (SVFs) purified from human subcutaneous adipose tissue and inguinal adipose tissue of obese and diabetic (Lepr(db/db)) mice were treated with 50 ng of MCP-1 and plasma from control (Lepr(+/+)) mice supplemented with 10 ng or 50 ng of MCP-1. Treatment of SVFs from human subcutaneous adipose tissues with 50 ng of MCP-1 significantly increased AdipoQ, DPP4, peroxisome proliferator-activated receptor gamma (PPARgamma), fatty-acid-binding protein (FABP4), and SERBF1 mRNA expression. MCP-1-supplemented plasma increased adiponectin, CCAAT-Enhancer-binding protein alpha (C/EBPalpha), DPP4, IL-33, and PDGFRalpha mRNA expression and adiponectin and DPP4 protein expression, while decreasing the expression of IL-10 mRNA in SVFs compared with the levels in the plasma treatment group. MCP-1-supplemented plasma was shown to increase PPARgamma, PPARgamma2, adiponectin, DPP4, and FABP4 and decrease IL-10 mRNA expression in PDGFRalpha cells from adipose tissue. Meanwhile, MCP-1-supplemented plasma increased MCP-1, PDGFRalpha, TNFalpha, adiponectin, and IL-1beta and decreased IL-10 and FOXP3 mRNA expression in DPP4 cells. Moreover, the injection of MCP-1-supplemented plasma into adipose tissue increased the proportion of DPP4(+) cells among PDGFRalpha(+) cells from adipose tissue and plasma adiponectin levels of Lepr(db/db) mice compared with the levels in the plasma injection group. Our results demonstrate that DPP4(+) cells are important adipose progenitor cells. Stimulation of DPP4 with MCP-1 increases adipogenesis-related gene expression and the population of DPP4(+) cells among PDGFRalpha(+) cells in SVFs and blood adiponectin levels. DPP4 stimulation could be a novel therapy to increase local adipogenesis and systemic adiponectin levels. FAU - Lai, Hsiao-Chi AU - Lai HC AUID- ORCID: 0000-0002-8332-8970 AD - Department of Surgery, Kaohsiung Veterans General Hospital, No. 386, Ta-Chung 1st Road, Kaohsiung 813, Taiwan. AD - Institute of Emergency and Critical Care Medicine, National Yang Ming Chiao Tung University, No. 155, Sec. 2, Linong Street, Taipei 112, Taiwan. FAU - Chen, Pei-Hsuan AU - Chen PH AD - Department of Surgery, Kaohsiung Veterans General Hospital, No. 386, Ta-Chung 1st Road, Kaohsiung 813, Taiwan. AD - Institute of Emergency and Critical Care Medicine, National Yang Ming Chiao Tung University, No. 155, Sec. 2, Linong Street, Taipei 112, Taiwan. FAU - Tang, Chia-Hua AU - Tang CH AD - Department of Surgery, Kaohsiung Veterans General Hospital, No. 386, Ta-Chung 1st Road, Kaohsiung 813, Taiwan. FAU - Chen, Lee-Wei AU - Chen LW AUID- ORCID: 0000-0002-3583-1248 AD - Department of Surgery, Kaohsiung Veterans General Hospital, No. 386, Ta-Chung 1st Road, Kaohsiung 813, Taiwan. AD - Institute of Emergency and Critical Care Medicine, National Yang Ming Chiao Tung University, No. 155, Sec. 2, Linong Street, Taipei 112, Taiwan. AD - Department of Biological Sciences, National Sun Yat-Sen University, No. 70, Lien-Hai Road, Kaohsiung 804, Taiwan. LA - eng GR - KSVGH112-082/Kaohsiung Veterans General Hospital/ PT - Journal Article DEP - 20231108 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 0 (Adiponectin) RN - EC 3.4.14.5 (Dipeptidyl Peptidase 4) RN - 130068-27-8 (Interleukin-10) RN - 0 (PPAR gamma) RN - EC 2.7.10.1 (Receptor, Platelet-Derived Growth Factor alpha) RN - 0 (RNA, Messenger) RN - EC 3.4.14.5 (Dpp4 protein, mouse) SB - IM MH - Animals MH - Humans MH - Mice MH - *Adipogenesis/genetics MH - *Adiponectin/metabolism MH - Dipeptidyl Peptidase 4/genetics MH - Gene Expression MH - Interleukin-10/genetics MH - PPAR gamma/metabolism MH - Receptor, Platelet-Derived Growth Factor alpha/genetics MH - RNA, Messenger/metabolism MH - Stromal Cells/metabolism PMC - PMC10671339 OTO - NOTNLM OT - FOXP3 OT - IL-10 OT - PDGFRalpha OT - adipogenesis OT - adipose COIS- The authors declare no conflict of interest. EDAT- 2023/11/25 12:42 MHDA- 2023/11/27 16:18 PMCR- 2023/11/08 CRDT- 2023/11/25 01:15 PHST- 2023/09/17 00:00 [received] PHST- 2023/11/01 00:00 [revised] PHST- 2023/11/04 00:00 [accepted] PHST- 2023/11/27 16:18 [medline] PHST- 2023/11/25 12:42 [pubmed] PHST- 2023/11/25 01:15 [entrez] PHST- 2023/11/08 00:00 [pmc-release] AID - ijms242216101 [pii] AID - ijms-24-16101 [pii] AID - 10.3390/ijms242216101 [doi] PST - epublish SO - Int J Mol Sci. 2023 Nov 8;24(22):16101. doi: 10.3390/ijms242216101.