Extracellular vesicles in non-alcoholic and alcoholic fatty liver diseases

Abstract

Fatty liver diseases, non-alcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD) are the most common causes of chronic liver disease around the world. NAFLD and ALD can progress towards a more severe form of the disease, including as non-alcoholic steatohepatitis (NASH) and alcoholic steatohepatitis (ASH). In both instances central pathogenic events include hepatocyte death, liver inflammation, pathological angiogenesis, and fibrosis, followed by cirrhosis and cancer. Over the last few years, extracellular vesicles (EVs) have been identified as effective cell-to-cell communicators that contain a cell- and stress-specific cargo from the cell of origin and are capable of transferring this cargo to a target or acceptor cell. In this review, we focus on the growing evidence supporting a role for EVs in the pathophysiology of NASH and ASH as well as their potential roles as targets for novel biomarkers for these conditions.

Extracellular Vesicles in NAFLD/ALD: From Pathobiology to Therapy

“…A number of studies have demonstrated a role of EVs in both the pathogenesis and progression of NAFLD [14,15]. Triggering of inflammation and fibrosis development are key for progression from isolated steatosis (also referred as NAFL or non-NASH fatty liver) to nonalcoholic steatohepatitis (NASH), which is hallmarked by the presence of hepatocyte ballooning as a reflection of ongoing liver injury and death [36].…”

“…In this regard, it has been observed that hypoxia determines that fat-laden hepatocytes release EVs able to signal KCs, evoking proinflammatory phenotypes in these cells, a phenomenon that may explain the aggravating effect of obstructive sleep apnea syndrome on NAFLD [71]. Thus, it seems clear that lipotoxic injury of hepatocytes determines EV release, promoting inflammation through activation and recruitment of macrophages [14], with clear implications for the triggering of inflammation in NAFLD/NASH [36]. In addition, hepatocyte-derived EVs may promote HSC activation [47,72] in experimental models of NAFLD/NASH.…”

“…Recent studies have focused on the role of EVs in ALD [11,14,84,85]. Both hepatocyte-and monocyte-derived EVs have been postulated to regulate macrophage differentiation, thereby promoting inflammation in alcoholic hepatitis (AH) [24,41,55,72,86].…”

“…In the field of hepatology, EVs have recently emerged as novel players in the pathogenesis and progression of several conditions [11][12][13], including the two most common liver diseases worldwide: nonalcoholic liver disease (NAFLD) and alcoholic liver disease (ALD) [14]. Specifically, recent studies point to a significant role of EVs in modulating injury, amplifying inflammation, and promoting liver fibrosis in both NAFLD and ALD [15][16][17].…”

Effect of circulating exosomes derived from normal-weight and obese women on gluconeogenesis, glycogenesis, lipogenesis and secretion of FGF21 and fetuin A in HepG2 cells

“…secreted from different cell types send "pro-inflammatory/pro-fibrotic" signals to the liver [15,16]. For instance, Koeck et al observed that exosomes secreted from the visceral adipose tissues of obese patients cause impairment of the TGF-β pathway, which in turn leads to hepatic fibrosis [17].…”