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In experimental models ithas been observed that leptin exert a double effect on NAFLD. It could exert aprotective role by hepatic steatosis, especially in the early stages ofdesease, but it could also act as inflammatory and fibrinogenic factor as thedisease persists or progresses.  It hasbeen proposed that the adipokines, such as leptin, may have a bidirectionalrole in IR and NAFLD. Many alterations of adipokines during the expansion ofadipose tissue are compensatory with the aim of providing beneficial effects,but they may simultaneously cause harmful effects.

In this regard, it has been suggestedthat with increasing fat mass leptin levels increase as a compensatorymechanism in order to limit the expansion of fat mass and thus preserve insulinsensitivity. In this manner leptin exerts an anti steatotic effect onhepatocytes. On the contrary, in the case in which adipose tissue continues toexpand it is observed to a failure of leptin in compensating for an increase ofthe IR and steatosis beyond a certain limit. In this context, leptin can exertharmful effects by acting as a fibrinogenic and pro-inflammatory adipokine.Then the leptin in this context may interact with other factors that contributeto the progression of NAFLD such as the regucalcin, which is considered toprevent the progression of NAFLD, under adjusting the leptin level both in thehepatocytes that in the adipose tissue. Leptin is considered to underlie ofobesity cancer link. It is produced in proportion to the amount of fat mass andexerts an action of cell mitogenesis, growth and motility.

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Within the adiposetissue mature adipocytes secrete both adiponectin that leptin, insteadpreadipocytes favor a higher secretion of leptin. In fact in obese subjects inwhich there is an increase in the population of pre-adipocytes can be observedto an increase in leptin showing pro- angiogenic and pro-mitogenic properties.Again, high levels of leptin bring to stimulation of the monocytes intomacrophages favoring in this manner the state of chronic inflammationassociated with obesity.

Summarizing, leptin plays an important role in promotinga wide variety of diseases by increasing the expression of anti-apoptoticproteins, pro-inflammatory cytokines such as TNF-a and IL-6, angiogenic factorssuch as VEGF and also HIF-1a.

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