Table 1.

Selected FASN target genes involved in the insulin-glucose metabolic axis.1

Genex-Fold changeFunction
CAV1 (caveolin 1, caveolae protein, 22kDa)+6.6Effective insulin signaling in the adipocyte may be strictly dependent on location of at least 2 insulin-responsive elements to caveolae (insulin receptor and the glucose transporter GLUT4), as well as on a direct functional interaction between caveolin-1 and the insulin receptor
ITGB1 [integrin, beta 1 (fibronectin receptor, beta polypeptide, antigen CD29 includes MDF2, MSK12)] and ITGA6 (integrin, alpha 6)+6.0 and 7.0Members of the integrin family of receptors that regulate cell migration through interactions with insulin growth factors (IGFs) and IGF binding proteins (IGFBPs)
TNC (tenascin C)+7.3TNC participates in the ability of IGFBPs to modify IGF actions dependent on the amount that is associated to the extracellular matrix
SPP1 (secreted phosphoprotein 1)+7.6A bone-derived factor playing a key role in the recently emerged role of the skeleton as an endocrine organ with effects on body weight control and glucose homeostasis
IGFBP3 (insulin-like growth factor binding protein 3)+7.9IGFBP-3, the major circulating carrier protein for IGFs, modulates IGF actions and also possesses intrinsic activities. In vitro and in vivo findings suggest that IGFBP-3 has potent insulin-antagonizing capability, supporting its role in cytokine-induced insulin resistance and other mechanisms involved in the development of type 2 diabetes
THBD (thrombomodulin)+8.0THBD has been shown to play a role in the association between insulin resistance with accelerated atherosclerosis, especially coronary heart disease. Plasma-soluble THBD appears to reflect endothelial damage in the state of insulin resistance in patients with type 2 diabetes
THBS1 (thrombospondin 1)+8.9An antiangiogenic factor and regulator of transforming growth factor β activity, obesity, adipose inflammation, and insulin resistance; THBS1 is a true adipokine that is highly expressed in obese, insulin-resistant individuals, and is highly correlated with adipose inflammation
TGFB1 (transforming growth factor, beta 1)+9.3TGFB1 is a potent growth inhibitor of normal breast epithelia that is able to indirectly mediate its growth-inhibitory effects by inducing the secretion of IGFBP3, which sequesters and prevents IGFs from binding and transducing mitogenic signals through the IGF receptors
IGF2 [insulin-like growth factor 2 (somatomedin A)]+9.9This peptide produces marked insulinlike effects in various targets tissues
IGFBP1 (insulin-like growth factor binding protein 1)+10.0IGFBP-1 is negatively regulated by insulin. Thus, elevated insulin and body fat are associated with decreased IGFBP-1 levels cross-sectionally, further indicating that IGFBP-1 levels may be altered through change in insulin over time and are a potential serum marker of insulin resistance
GPC3 (glypican 3)+11.2GPC3 is a cell-surface heparan-sulfate proteoglycan that acts as a growth suppressor by sequestering or downregulating IGF2. GPC2 may play roles in glucose transport through its direct interaction with GLUT4
SPARC [secreted protein, acidic, cysteine-rich (osteonectin)]+11.3Elevated adipocyte tissue expression of SPARC (secreted protein acidic and rich in cysteine), which markedly occurs is different animal models of obesity, is a newly identified autocrine/paracrine factor that could affect key functions in adipose tissue physiology and pathology