Gene expression profiles indicate tissue-specific obesity regulation changes and strong obesity relevant tissues.

BACKGROUND: With the growing evidence that other tissues, apart from adipose, could have strong relevance to obesity, it is necessary to comprehensively understand the relationship between obesity and other tissues, and to point out the most relevant tissues.

METHODS: There were 549 participants with 20 different tissue types involved in this study. We firstly employed both Spearman's correlation test and WGCNA (weighted correlation network analysis) to identify body mass index (BMI)-related genes. Subsequently, we performed enrichment analyses with obesity genes and pathways to see the different regulation patterns among tissues. In addition, we compared obesity genes identified by genome-wide association studies (GWAS) with BMI-related genes to find the overlapping proportion in each tissue. Finally, we integrated preceding results to identify six strong obesity relevant tissues and indicate three categories to represent different obesity relevant tissues.

RESULTS: Statistical analyses revealed diverse BMI-related genes and tissue-specific enrichment patterns among tissues. Comparison between BMI-related genes and GWAS findings showed tissue-specific expression changes of GWAS genes. Ultimately, six tissues that showed predominant performance in enrichment analyses and significantly embraced GWAS genes were referred to as strong obesity relevant tissues, including adipose, esophagus, nerve, pancreas, pituitary and skin. We also proposed three categories to represent different obesity relevant tissues.

CONCLUSIONS: We performed the first study to investigate the BMI-related gene expression changes across 20 tissues at the same time. With valid data analyses and comparison with GWAS findings, our study provides a holistic view of how different tissues correlate with obesity, and proposes target tissues for obesity pathogenesis investigation.