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In experimental models it
has been observed that leptin exert a double effect on NAFLD. It could exert a
protective role by hepatic steatosis, especially in the early stages of
desease, but it could also act as inflammatory and fibrinogenic factor as the
disease persists or progresses.  It has
been proposed that the adipokines, such as leptin, may have a bidirectional
role in IR and NAFLD. Many alterations of adipokines during the expansion of
adipose tissue are compensatory with the aim of providing beneficial effects,
but they may simultaneously cause harmful effects. In this regard, it has been suggested
that with increasing fat mass leptin levels increase as a compensatory
mechanism in order to limit the expansion of fat mass and thus preserve insulin
sensitivity. In this manner leptin exerts an anti steatotic effect on
hepatocytes. On the contrary, in the case in which adipose tissue continues to
expand it is observed to a failure of leptin in compensating for an increase of
the IR and steatosis beyond a certain limit. In this context, leptin can exert
harmful effects by acting as a fibrinogenic and pro-inflammatory adipokine.
Then the leptin in this context may interact with other factors that contribute
to the progression of NAFLD such as the regucalcin, which is considered to
prevent the progression of NAFLD, under adjusting the leptin level both in the
hepatocytes that in the adipose tissue. Leptin is considered to underlie of
obesity cancer link. It is produced in proportion to the amount of fat mass and
exerts an action of cell mitogenesis, growth and motility. Within the adipose
tissue mature adipocytes secrete both adiponectin that leptin, instead
preadipocytes favor a higher secretion of leptin. In fact in obese subjects in
which there is an increase in the population of pre-adipocytes can be observed
to an increase in leptin showing pro- angiogenic and pro-mitogenic properties.
Again, high levels of leptin bring to stimulation of the monocytes into
macrophages favoring in this manner the state of chronic inflammation
associated with obesity. Summarizing, leptin plays an important role in promoting
a wide variety of diseases by increasing the expression of anti-apoptotic
proteins, pro-inflammatory cytokines such as TNF-a and IL-6, angiogenic factors
such as VEGF and also HIF-1a.

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