Targeting adipose remodeling: Synergistic mechanisms of drugs and adipose-derived stem cells in obese type 2 diabetes mellitus

Table 4 Secretory factors of adipose-derived stem cells and their metabolic and immunomodulatory effects in target tissues

Category of secretion	Representative molecules/miRNAs	Main target tissues or cells	Typical receptors/signaling pathways	Expected metabolic and inflammatory effects
Cytokines	IL-10, TGF-β, VEGF, HGF	VAT, SAT, liver, skeletal muscle, macrophages	JAK1/Tyk2-STAT3; SMAD2/3; VEGFR2-PI3K/Akt	Inhibit NF-κB and JNK-mediated inflammation; promote angiogenesis and tissue repair; enhance insulin signaling throughput
Exosomal miRNAs	miR-223-3p, miR-29a, miR-155, miR-210	Hepatocytes, adipocytes, macrophages	Target E2F1, SOCS1/STAT1, SHIP1, IRAK1/NF-κB	Alleviate hepatic steatosis and fibrosis; modulate macrophage polarization; promote adipose browning and adiponectin secretion
Growth/chemotactic factors	Ang-1, FGF, IGF-1, MCP-1	Vascular endothelium, fibroblasts, immune cells	Tie2-Akt; FGFR-MAPK; CCR2	Promote vascular remodeling; chemotactic regulation of immune cells; improve tissue microcirculation
Antioxidant regulatory axis	PGC-1α-induced upregulation of SOD2, UCP1	White/brown adipocytes	PGC-1α-TFAM; UCP1-uncoupling	Enhance mitochondrial biogenesis and oxidative phosphorylation; reduce ROS load; increase energy expenditure

miRNA: MicroRNA; IL-10: Interleukin 10; TGF-β: Transforming growth factor beta; VEGF: Vascular endothelial growth factor; HGF: Hepatocyte growth factor; VAT: Visceral adipose tissue; SAT: Subcutaneous adipose tissue; JAK1: Janus kinase 1; Tyk2: Tyrosine kinase 2; STAT3: Signal transducer and activator of transcription 3; SMAD2/3: Mothers against decapentaplegic homolog 2/3; VEGFR2: Vascular endothelial growth factor receptor 2; PI3K: Phosphoinositide 3-kinase; Akt: Protein kinase B; NF-κB: Nuclear factor kappa B; JNK: C-Jun N-terminal kinase; E2F1: E2F transcription factor 1; SOCS1: Suppressor of cytokine signaling 1; SHIP1: SH2-containing inositol phosphatase 1; IRAK1: Interleukin-1 receptor-associated kinase 1; Ang-1: Angiopoietin 1; FGF: Fibroblast growth factor; IGF-1: Insulin-like growth factor 1; MCP-1: Monocyte chemoattractant protein 1; Tie2: Tyrosine kinase with immunoglobulin-like and endothelial growth factor-like domains 2; FGFR: Fibroblast growth factor receptor; MAPK: Mitogen-activated protein kinase; CCR2: C-C chemokine receptor type 2; PGC-1α: Peroxisome proliferator-activated receptor gamma coactivator 1-alpha; SOD2: Superoxide dismutase 2; UCP1: Uncoupling protein 1; TFAM: Transcription factor A, mitochondrial; ROS: Reactive oxygen species; miR: MicroRNA.