['Leptin gene expression is highly correlated with cellular lipid content in adipocytes but the transcriptional mechanisms controlling leptin expression in\xa0vivo are poorly understood. In this report, we set out to identify cis- and trans-regulatory elements controlling leptin expression.', 'Leptin-BAC luciferase transgenic mice combining with other computational and molecular techniques were used to identify transcription regulatory elements including a CCAAT-binding protein Nuclear Factor Y (NF-Y). The function of NF-Y in adipocyte was studied in\xa0vitro with 3T3-L1 cells and in\xa0vivo with adipocyte-specific knockout of NF-Y.', 'Using Leptin-BAC luciferase mice, we showed that DNA sequences between\xa0-22\xa0kb and\xa0+8.8\xa0kb can confer quantitative expression of a leptin reporter. Computational analysis of sequences and gel shift assays identified a 32\xa0bp sequence (chr6: 28993820-2899385) consisting a CCAAT binding site for Nuclear Factor Y (NF-Y) and this was confirmed by a ChIP assay in\xa0vivo. A deletion of this 32\xa0bp sequence in the\xa0-22\xa0kb to\xa0+8.8\xa0kb leptin-luciferase BAC reporter completely abrogates luciferase reporter activity in\xa0vivo. RNAi mediated knockdown of NF-Y interfered with adipogenesis in\xa0vitro and adipocyte-specific knockout of NF-Y in mice reduced expression of leptin and other fat specific genes in\xa0vivo. Further analyses of the fat specific NF-Y knockout revealed that these animals develop a moderately severe lipodystrophy that is remediable with leptin therapy.'] Is nuclear Factor-Y an adipogenic factor that regulates leptin gene expression?