By Atta-ur- Rahman; M Iqbal Choudhary

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12) 38 Anti-Obesity Drug Discovery and Development, Vol. 2 Sabán-Ruíz et al. The VMT understands vascular damage as occurring in a parallel way to metabolic damage, and not as a mere consequence of the first one. Moreover, this theory incorporates metabolic elements of paramount importance when compared with the conventional theory, which relies basically upon IR alone. The presence of MetS, which is much more prevalent in obese subjects, amplifies the pathogenic phenomena in both directions. In the case of T2DM, only present if there is a genetic susceptibility of β cells, it will enhance this even more due to the fact that this dysfunction incorporates a new key element, to configure an integrated “puzzle” of “health damage”.

In addition to ER stress, the Forkhead Transcription Factor (FOX01), oxidative stress and GPR40 receptor are also involved in β-cell dysfunction. FOX Family (named Forkhead by a couple of ectopic structures in drosophila) is a set of proteins also called "winged helix" for his appearance in the crystallographic study. While they are genes in invertebrates, in mammals they are a family of transcription factors. Unlike other transcription factors, it does not contain homeodomains or zinc-fingers, but a distinct type of DNA-binding region including around 100 amino acids.

The endothelial MCP-1 is stimulated by leptin, so that adipocyte has a double role in this process. On the other hand, MCP-1 activates the circulating monocyte, increasing the expression of CD11-b. Once the monocyte is “called”, it leaves the vessel and enters into the adipose tissue. In order to remain within the WAT, the monocyte requires the presence of the macrophage inhibitory factor (MIF) and the macrophage colony-stimulating factor (M-CSF). An Approach to Obesity as a Cardiometabolic Anti-Obesity Drug Discovery and Development, Vol.

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