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

Table 6 Targeted pathways and metabolic effects of adipose-derived stem cell-derived exosomal microRNAs

miRNA	Major direct target genes/pathways	Target tissues/cells	Metabolic or inflammatory effects	Evidence type1
miR-223-3p	E2F1 → Inhibits adipogenesis/fibrosis	Hepatocytes	Reduces hepatic lipid accumulation and fibrosis	HFD mice (in vivo)/HepG2 (in vitro)
miR-29a	SOCS1/STAT1	Macrophages	Inhibits M1 polarization, decreases TNF-α/IL-6	LPS-stimulated RAW264.7/mice
miR-155	SHIP1/SOCS1	Macrophages	Promotes M1 polarization, amplifies inflammation	Functional antagonism in vitro
miR-34a	SIRT1/FGF21	Liver and adipose tissue	Inhibits browning, promotes adipogenesis	DIO mice (in vivo)
miR-210	IRAK1/NF-κB	Liver, skeletal muscle	Reduces inflammation, improves insulin sensitivity	db/db mice (in vivo)
miR-126	IRS-1/PI3K-Akt	Endothelial cells	Promotes angiogenesis, improves insulin signaling	STZ rats (in vivo)/HUVEC

¹Evidence types include in vivo animal models and in vitro cell line experiments. miRNA: MicroRNA; E2F1: E2F transcription factor 1; SOCS1: Suppressor of cytokine signaling 1; STAT1: Signal transducer and activator of transcription 1; SHIP1: SH2-containing inositol phosphatase 1; SIRT1: Sirtuin 1; FGF21: Fibroblast growth factor 21; IRAK1: Interleukin-1 receptor-associated kinase 1; NF-κB: Nuclear factor kappa B; IRS-1: Insulin receptor substrate 1; PI3K: Phosphoinositide 3-kinase; Akt: Protein kinase B; TNF-α: Tumor necrosis factor-alpha; IL-6: Interleukin 6; HFD: High-fat diet; HepG2: Human hepatocellular carcinoma cell line; LPS: Lipopolysaccharide; RAW264.7: Murine macrophage cell line; DIO: Diet-induced obesity; db/db: Diabetic obese (leptin receptor-deficient) mouse model; STZ: Streptozotocin; HUVEC: Human umbilical vein endothelial cells; M1: Classically activated macrophage (proinflammatory phenotype); miR: MicroRNA.