ENAapplication/xmlftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR108/051/SRR10850851/SRR10850851.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR108/052/SRR10850852/SRR10850852.fastq.gzprimaryOK200GenomicsSysgem Genomics, Life Sciences, Ewha Womans Universityhttps://www.ebi.ac.uk/ena/browser/view/PRJNA599946Mus musculusRecently white adipose tissues (WAT) have been shown to be able to generate heat upon cold exposure through the expression of uncoupling protein-1 (UCP1), a molecule regulating mitochondrial proton gradient. Although the role of UCP1 has been extensively investigated in adipocytes, it is currently unknown whether UCP1 in the microenvironment of WAT such as adipose-tissue macrophages (ATM) could play a role in thermogenesis. Given the critical role of hypoxia in regulating obesity and insulin resistance, we challenged our myeloid-specific hypoxia-inducible factor-1α (Hif-1α) knockout (KO) mice to high fat diet and observed that these mice were not only protected from diet-induced obesity but also resistant to the body temperature changes upon cold exposure, the latter effect being completely lost upon surgical removal of WAT. Mechanistically, ATM deficient for HIF-1α generated heat production through increased expression of UCP1 and increased mitochondrial functions, all of which lead to an enhanced lipolysis in neighboring adipocytes. Lastly, we observed a number of co-localized areas between UCP-1 and CD68 in WAT of lean mice as well as individuals whereas such areas were not observed in an obese mice or human subjects. In conclusion, we demonstrate a novel mechanism by which ATM regulate obesity through UCP1-mediated heat generation. Overall design: The investigation of gene expression change in FACS-sorted adipose tissue macrophages (ATM) from hMRP8cre+ Hif-1αfl/fl ApoE-/- mice or hMRP8cre- Hif-1αfl/fl ApoE-/- mice.xref:PubMed:39473019ENAfalseHeat production from adipose-tissue macrophages regulates lipolysis and diet-induced obesityHeat production from adipose-tissue macrophages regulates lipolysis and diet-induced obesity2025-09-242024-12-19PRJNA599946GSE1432981009039473019