GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE333nnn/GSE333670/primaryOK200TranscriptomicsMus musculusExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE333670GEOGSEfalseSOX4 Drives a Cancer-Associated Fibroblast-like Transition in Adipose Stromal Cells to Promote Metabolic DiseaseAdipose tissue dysfunction drives metabolic disease in obesity and is characterized by impaired adipogenesis, chronic inflammation, and fibrosis. Here, we define a pathogenic cancer-associated fibroblast-like (CAF-like) stromal population that accumulates in visceral adipose tissue during obesity under the control of the transcription factor SOX4. Obesity and TGFβ signaling induce SOX4 in mesenchymal stromal cells (MSCs), where it promotes a CAF-like transcriptional program while suppressing adipogenic differentiation. SOX4 activation in mouse MSCs exacerbated adipose inflammation, fibrosis, and glucose intolerance independently of adiposity. Conversely, Sox4 deletion reduced adipose immune cell accumulation and improved glucose homeostasis during obesity. We further identify the growth factor Midkine (MDK) as a SOX4-regulated paracrine effector of CAF-like cells. MDK inhibition in obese mice reduced adipose tissue inflammation and improved metabolic function, whereas MDK activation promoted inflammatory remodeling of adipose tissue. In human adipose tissue, SOX4 and MDK expression were elevated in type 2 diabetes, and SOX4 activated a CAF-like transcriptional program in human MSCs. Overall, these findings identify a TGFβ-SOX4-MDK axis that drives pathogenic stromal reprogramming in adipose tissue and contributes to metabolic disease.2026/05/28GSE333670GSM9770639GSM977064024247333670Mus musculus