RNAseq analysis of adipose tissue transcriptomes from wild-type and FNIP1 adipocyte specific knockout (FNIP1-AKO) mice

Activation of thermogenesis in brown and beige adipocytes upon activation by external stimuli burns fuel energy as heat. Owing to its remarkable benefits on metabolic health and its demonstrated presence in adult humans, beige adipocytes holds great promise to combat obesity and metabolic diseases. Folliculin interacting protein 1 (FNIP1) is an adaptor protein originally identified through its interaction with folliculin (FLCN) and AMPK. To investigate the physiological role of FNIP1 in adipose tissue in vivo, we generated adipocyte-specific FNIP1 deficient mice (referred to as FNIP1-AKO) by crossing mice bearing a conditional Fnip1 allele with introns 5 and 6 floxed (Fnip1 lox/lox) with the adiponectin promoter–driven Cre mice. We performed transcriptome analysis by whole-genome gene expression profiling experiments in inguinal white adipose tissue (iWAT) from both wild-type (WT) and FNIP1-AKO mice. We were particularly interested in the subset of genes that were up-regulated in the FNIP1-AKO mice. Gene ontology (GO) analysis revealed that the primary up-regulated genes were mitochondrial and lipid metabolism-related genes. Gene expression validation studies demonstrated that a broad array of genes involved in thermogenic and mitochondrial oxidative program was induced in FNIP1-AKO iWAT. Together, the transcriptional profiling results indicate that loss of FNIP1 activate thermogenic program in white adipocytes. Overall design: Inguinal white adipose tissue mRNA profiles of 8-week-old WT and FNIP1-AKO mice were generated by deep sequencing, in duplicate, using Illumina HiSeq 4000.