Mediators volume. In the condition of obesity is

Mediators derived by the
majority from adipocytes as adiponectin and TNF-a could be involved in some of
these processes and therefore these adipokines might represent a possible link
between obesity and related disorders with the development of tumors both
intra- and extra hepatic. In order to exert its anti-carcinogenic action,
adiponectin stops the growth of colon cancer cells through the AMPc-activated
protein kinase (AMPK) activation and stimulating the caspase-dependent pathway
in order to activate the apoptosis of endothelial cells. Moreover adiponectin
it can also act directly by inhibiting TNF-a, which is involved in both tumor
proliferation and angiogenesis. Given that in patients with NAFLD were found
low levels of adiponectin, all the mechanisms described above represent an
important link between NAFLD and development of cancer in both gastrointestinal
that extra intestinal sites. Moreover low levels of adiponectin have been
associated with an increased risk of onset of colorectal cancer. Lower levels
of adiponectin imply an increase of insulin due to a marked insulin resistance
and in turn increased IGF-1. Through the binding of insulin to its receptor,
the insulin becomes an important factor in the regulation of cell
proliferation, apoptosis and increasing the production of VEGF, an angiogenic
factor that supports tumor growth. although there are still disputes, it was
observed that in patients with NAFLD adiponectin levels increase after a major
weight loss and lifestyle changes. However it found order to have a significant
increase of adiponectin it is necessary a significant weight loss (> 10%).

The pro-carcinogenic
effects of leptin, especially in the presence of low levels of adiponectin have
been extensively studied. It was observed that in obese animal models leptin
acts as a growth factor for colorectal cancer especially in the initial stages
through the activation of signal transducer and activator of transcription 3
(STAT3) pathway. Through the activation of mitogen-activated protein kinase
(MAPK) pathway, leptin is able to promote the motility and invasiveness of
colorectal cancer cells. Leptin production is due mainly to limit the
continuous entry of fatty acids in adipocytes hypertrophic, choice of defense
necessary to prevent the cell death due to an excessive volume. In the
condition of obesity is established a state of leptin resistance, and then the
action ensured by this adipocytokine cannot be explicated.