Extra-Thyroidal Action of TSH on Adipocyte Insulin Signaling

Title: Extra-Thyroidal Action of TSH on Adipocyte Insulin Signaling
Authors: Felske, David
Date: 2015
Abstract: In subclinical hypothyroidism (SH), high levels of circulating thyroid stimulating hormone (TSH) maintain normal thyroid hormone levels, despite mild thyroid failure. SH is associated with cardiovascular disease and insulin resistance, although the underlying pathophysiology is not fully understood. We hypothesized that TSH may inhibit insulin action in adipocytes. To investigate this relationship, we studied primary human differentiated adipocytes. Abdominal subcutaneous adipose tissue samples were obtained (approved by OHSN-REB) from 16 weight-stable patients undergoing elective abdominal surgery. We stimulated adipocytes differentiated from stromal preadipocytes with 5 mU/ml TSH and/or 100 nM insulin, and assessed acute insulin signaling, lipogenesis and glucose uptake. Immunoblot analysis revealed that TSH suppressed insulin-stimulated Akt phosphorylation by 45% (n=5; p = 0.01). When adipocytes were pre-incubated with conventional protein kinase C (cPKC) inhibitor Gö6976, TSH inhibition was blocked. Our data indicate that TSH inhibits insulin-stimulated lipogenesis (up to 37%), but depends on BMI. Insulin-stimulated glucose uptake was enhanced by 36% and also correlated with BMI. This data suggests that TSH can modulate adipocyte insulin signaling.
URL: http://hdl.handle.net/10393/31906
CollectionThèses, 2011 - // Theses, 2011 -