MON-LB018 Depot-Specific Differences in Adipose Tissue Morphology with Laron Syndrome

Abstract

In 1997, our laboratory generated GH receptor gene-disrupted mice (GHR−/−), a mouse model of GH resistance that resembles the human condition termed Laron Syndrome (LS). These mice have provided countless insights into the numerous actions of GH. In particular, adipose tissue (AT) abundance and function have been extensively studied in these mice. Because GH is a major lipolytic hormone, GHR-/- mice have an increase in body fat percentage throughout life, with a notable and disproportionate increase in subcutaneous depots. Many other characteristics of adipose tissue in these mice have been evaluated, including immune cell infiltration, adipokine expression, fibrosis, senescence and gene expression analysis. Consistently, the subcutaneous depot is most dramatically altered by the absence of GH action in GHR-/- mice. While these mice provide an opportunity to routinely analyze multiple AT depots, their relevance to the clinical condition remains unexplored where invasive sampling of multiple AT depots in humans is not typically feasible. In order to begin addressing the clinical relevance of our mouse data, the purpose of this study was to compare AT morphology and adipocyte size in subcutaneous and visceral AT from a female patient with LS undergoing Roux-en-Y gastric surgery to that of the AT data collected from a control female patient. The patient with LS had a BMI of 43.3; the control patient had a comparable BMI of 39.5. Glucose and insulin levels were comparable between the patients, with glucose values of 104 mg/dl and 107 mg/dl, and insulin values of 10 µU/ml and 15 µU /ml for the patient with LS and the control patient, respectively. Samples of subcutaneous AT were taken from the lower abdominal wall and visceral AT from the greater omentum during the surgery. Tissue was immediately frozen or fixed in buffered formalin, paraffin embedded and processed for histological analyses. As our results in mice would suggest, we observed a more significant enlargement in subcutaneous versus visceral adipocytes from the patient with Laron syndrome. In addition, fibrosis appeared to be reduced to a greater extent in the subcutaneous depot. The difference in adipocyte size and fibrosis between the depots was not apparent in the control sample. While results from a single patient with LS compared to a control has obvious limitations, these valuable LS samples do provide initial evidence for a depot-specific alteration in AT in clinical populations comparable to what has been observed for the GHR-/- mice. In future studies, more extensive gene and protein analyses of the frozen tissue will provide additional insight as to the relevance of our GHR-/- data to clinical populations. Unless otherwise noted, all abstracts presented at ENDO are embargoed until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. s presented at a news conference are embargoed until the date and time of the news conference. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.