{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE296nnn/GSE296368/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"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=GSE296368"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Fatty Acid Esters of Hydroxy Fatty Acids (FAHFA) Derivatives as Dual Modulators of Lipid Metabolism and Gut Microbiome in Obesity","description":"Fatty Acid Esters of Hydroxy Fatty Acids (FAHFAs), endogenous lipids with anti-inflammatory and metabolic benefits, face challenges in clinical translation due to instability and high synthesis costs. This study introduces a scalable synthetic platform to engineer novel FAHFA derivatives with enhanced stability through bioisosteric modifications (e.g., amide, triazole bonds). Screening identified 12-TAASA and 12-HDTZSA as lead compounds, demonstrating potent inhibition of lipid uptake in hepatic cells without compromising glucose absorption. In a diet-induced obesity mouse model, oral administration of these derivatives reduced weight gain, improved glucose tolerance, and attenuated ectopic lipid deposition, rivaling the efficacy of semaglutide. Mechanistically, 12-TAASA and 12-HDTZSA remodeled the gut microbiome by enriching SCFA producing taxa. 12-TAASA also suppressed intestinal lipid absorption via transcriptomic regulation of key genes. These findings position synthetic FAHFAs as dual-action therapeutics, targeting both host lipid metabolism and gut microbiota dysbiosis, offering a promising strategy for obesity and metabolic disorders.","dates":{"publication":"2026/06/18"},"accession":"GSE296368","cross_references":{"GSM":["GSM8969229","GSM8969248","GSM8969237","GSM8969226","GSM8969236","GSM8969247","GSM8969239","GSM8969228","GSM8969249","GSM8969238","GSM8969227","GSM8969244","GSM8969233","GSM8969243","GSM8969232","GSM8969235","GSM8969246","GSM8969245","GSM8969234","GSM8969240","GSM8969242","GSM8969231","GSM8969241","GSM8969230"],"GPL":["28330"],"GSE":["296368"],"taxon":["Mus musculus"],"PMID":["[41485679]"]}}