Enhanced carbon tetrachloride-induced liver fibrosis in mice lacking adiponectin

Influence of Cannabis Use on Severity of Hepatitis C Disease

“…Antagonism of the CB1 receptor has been associated with reduced expression of the TGFβ1, a cytokine central to fibrosis production, and decreased stellate cell proliferation and increased apoptosis, all of which would be predicted to reduce fibrosis (9). Additionally, CB1 receptor antagonism has been associated with increased levels of adiponectin (26), an adipokine with antifibrotic properties in animal models (27). Thus, there are several potential mechanisms by which enhanced CB1 receptor expression or activity may lead to increased fibrosis.…”

Cellular and molecular mechanisms in liver fibrogenesis

“…Literature data indicate that adiponectin has predominantly hepato-protective and anti-fibrogenic effects in conditions of CLD [61], as shown in particular in the experimental model of fibrosis induced by chronic administration of CCl 4 [62]. Adiponectin has likely a protective role also in the context of NAFLD/NASH as shown by experiments in which pericellular fibrosis was found to be more severe in adiponectin-deficient mice (i.v., vs wild type mice) fed a high-fat diet [63].…”

“…In any case, adiponectin can act directly on HSC because these cells express both types of specific receptors [67,68]. Adiponectin has been reported to result in a suppression of both cytokine-stimulated proliferation and migration [62,67], to reduce TGFβ1-dependent effects [62] and even to favor induction of HSC apoptosis [68]. These anti-fibrogenic effects of adiponectin are likely to be mainly mediated through activation of AMP-activated protein kinase (AMPK), a critical downstream effector of AdipoR1 [67], although a single report suggested that blocking AdipoR2 expression worsened the development of fibrosis in a mouse model of dietary steatohepatitis [69].…”

Adiponectin Regulation of Stellate Cell Activation via PPARγ-Dependent and -Independent Mechanisms

“…Given that earlier studies showed that activation of stellate cells in culture is associated with a decline in expression of adiponectin, 25 we asked whether activation could be reversed by re-expression of adiponectin in cultured cells. First, we demonstrated that infection of stellate cells with a lentivirus containing an adiponectin construct led to increased production of adiponectin ( Figure 5A); additionally, a time-course experiment revealed that expression of adiponectin increased from 12 to 48 hours after infection ( Figure 5B).…”