Paper

Eric Bendel

Dr. Snow

5/9/2016

Effect of Extracellular Vesicles of Human Adipose Tissue on Insulin Signaling in Liver and

Muscle Cell

Abstract:

Insulin resistance (IR) plays and important role in obesity-induced cardiovascular disease. The

effects of adipose tissue-extracellular vesicles (AT-EVs) on insulin signaling was measured in

both muscle cells and liver cells. Based on this study, it was speculated that human AT-EVs can

positively or negatively affect insulin signaling in hepatocytes- possibly depending on adipokine

content- and thereby could contribute to systemic IR.

Background:

Insulin resistance (IR) and type 2 diabetes, which are often linked to obesity, greatly

increase the risks for cardiovascular disease (CD) and studies suggest that IR is a key process in

obesity-induced cardiovascular disease. Tissues such as the liver, fat, and muscle have a lesser

response to hormone insulin during insulin-resistant states; which results in things such as

impaired glucose uptake into muscles and impaired regulation of gluconeogenesis in the liver.

Visceral adipose tissue (VAT) is more strongly related to IR and CD than subcutaneous

AT (SAT). Disease contribution from VAT and SAT, though not fully understood, is probably

based on the fact that VAT has a more pronounced AT-inflammation than that of SAT.

Adipokines such as tumor necrosis factor alpha (TNF-a), interleukin-6 (IL-6), retinolbinding protein-4 (RBP-4), and macrophage migration inhibitory factor (MIF) are secreted by

inflamed AT. These adipokines act as inducers of IR. AT-inflammation induces lipolysis; which

increases systemic free fatty acids (FFA); which can activate the innate immune signaling

pathway in muscle and liver cells. This causes lipid-induced IR by accumulation of

diacylglycerols (DAG) and ceramides.

AT of obese mice (as well as human AT) secretes extracellular vesicles (EVs), which are

associated with systemic IR. EVs contain proteins, RNA, and lipids that...