{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE335nnn/GSE335244/"]},"type":"primary"},"statusCodeValue":200,"statusCode":"OK"}],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Mus musculus"],"gds_type":["Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE335244"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Myeloid MMP14 Couples Extracellular Proteolysis to Inflammatory and Metabolic Remodeling During Obesity","description":"Macrophages orchestrate tissue remodeling, inflammation, and metabolic dysfunction in obesity, yet how macrophage-intrinsic extracellular proteolysis integrates with immunometabolic reprogramming remains poorly defined. Matrix metalloproteinase-14 (MMP14), a membrane-anchored protease with broad matrix-remodeling capacity, is markedly induced during monocyte-to-macrophage differentiation and further upregulated in adipose tissue macrophages from high-fat diet (HFD)-fed mice. Pharmacologic inhibition or myeloid-specific deletion of Mmp14 impaired macrophage differentiation, proliferation, migration, and phagocytosis, and blunted pro-inflammatory activation in response to obese adipose tissue–derived cues. Mechanistically, MMP14 enhanced inflammatory programming in part by promoting endotrophin generation and amplifying TLR4-NF-κB signaling. In parallel, MMP14 reshaped macrophage lipid metabolism by suppressing lipolysis and fostering lipid accumulation, thereby modifying macrophage-derived metabolic signals to neighboring cells. In vivo, myeloid-specific Mmp14 deletion protected mice from HFD-induced insulin resistance, dyslipidemia, hepatic steatosis, and adipose tissue inflammation and fibrosis, while increasing energy expenditure and fatty acid utilization. Collectively, these findings identify macrophage MMP14 as a central node linking extracellular matrix remodeling to inflammatory and metabolic dysfunction in obesity.","dates":{"publication":"2026/06/22"},"accession":"GSE335244","cross_references":{"GSM":["GSM9808923","GSM9808924","GSM9808921","GSM9808922","GSM9808925","GSM9808926"],"GPL":["34328"],"GSE":["335244"],"taxon":["Mus musculus"]}}