Proteins Secreted by Visceral Adipose Tissue

Visceral adipose tissue is much more than a storage medium for excess energy. This realization came with the discovery in 1994 of leptin and its wide-ranging activities, which include reduction of appetite, angiogenesis, hematopoiesis, and bone formation [48-50] . Visceral adipose tissue is now recognized as an endocrine organ that releases a large number of biologically active molecules called adipokines, which have pleiotropic effects on a variety of metabolic pathways [48,51] . Proteins released from adipose tissue include regulators of inflammation, inducers of angiogenesis, and modulators of hypertension, among others. Visceral adipose tissue, in particular, has been implicated in the release of proteins responsible for metabolic syndrome and type 2 diabetes [52]. For this reason, evaluation of visceral adipose tissue, either alone or in comparison to subcutaneous adipose tissue, is of great interest [52,53].

As a pilot study of the eventual comparison of proteins secreted from visceral and subcutaneous adipose tissue, visceral adipose tissue was obtained from three obese patients undergoing gastric bypass surgery. The contents of the secretory apparatus were isolated from each subject and analyzed by LC-MS/MS to determine feasibility and yield, as well as to catalog the proteins and verify that known adipocyte-secreted proteins could be found. In a limited analysis, 155 proteins were identified, including many of the well-known adi-pokines. Among the proteins identified were cytokines (TGFb1; IL 25), acute-phase proteins (SPARC; lipocalin 2/NGAL), proteins that regulate blood pressure (angiotensinogen; ARTS-1), regulators of lipid metabolism (retinol-binding protein 4; lipoprotein lipase), and signaling molecules (galectin-1; prohibitin). Only 65 of the proteins were also found in one of three secreted-protein databases [54-56] . Although this could suggest that some of the proteins are contaminants, it could also point to the possibility that many secreted proteins are missed by conventional discovery methods that typically screen for proteins with an N - - erminal signal sequence -44,57] . Some well- known

TABLE 1 Five Proteins Found in the Secretory Apparatus of Human Visceral Adipose Tissue That Are Targets for Therapies in Clinical Trials

Target

Condition

Drug

MoA

Phase

Leucocyte

Acute respira

Depelestat

Inhibitor of elastase

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