Endocrine Abstracts

Introduction: It is now appreciated that peptide hormones encoded by the ghrelin gene, GHRL, have roles in many biological systems and cell types. In particular, the hormone ghrelin is a therapeutic target and clinical marker for a range of pathologies, including diet-induced and genetic obesity. High-quality transcriptome (RNA-seq) data sets generated by consortia, such as the Human Protein Atlas (HPA) and Encyclopedia of DNA Elements (ENCODE), now offer an opportunity to study the expression of any gene of interest in diverse cells and tissues.

Methods: We initially investigated GHRL expression in the human body by interrogating publically-available transcriptomes from 35 somatic cells and tissues, revealing relatively high expression in monocytes and associated tissues. In an effort to link monocyte GHRL more directly to functional outcomes, we next sought to compare its expression in 19 women before bariatric surgery and 12 weeks postoperatively.

Results: Monocyte GHRL expression was significantly reduced three months after bariatric surgery (P=0.0001 by Student’s t-test; n=19). A previous study of the same cohort demonstrated diminished obesity-induced inflammation and an altered interferon-γ (IFN-γ) pathway in adipose tissue and monocytes postoperatively. Here, we show that IFN-γ modulates GHRL expression in the monocyte-derived cell line THP-1 (P=0.0079 by Mann–Whitney U test; n=5).

Conclusion: While it is well-established that ghrelin plays a role in appetite regulation and energy balance, the function of GHRL in immune cells has hitherto remained enigmatic. Here, we present data that further supports cross-talk between the endocrine and immune systems. We put forward the hypothesis that monocyte GHRL-derived hormones are critical mediators of the brain-gut axis and monocyte-adipocyte cross-talk. Future longitudinal studies are needed to firmly establish a role for monocyte GHRL-derived peptides in successful bariatric surgery and obesity-associated pathologies, such as Prader-Willi syndrome and metabolic syndrome, in general.