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Review
. 2018 Feb;9(2):164-177.
doi: 10.1007/s13238-017-0436-0. Epub 2017 Jun 22.

New insight into inter-organ crosstalk contributing to the pathogenesis of non-alcoholic fatty liver disease (NAFLD)

Xu Zhang  1   2 , Xuetao Ji  1   2 , Qian Wang  3   4 , John Zhong Li  5   6
Affiliations
Review

New insight into inter-organ crosstalk contributing to the pathogenesis of non-alcoholic fatty liver disease (NAFLD)

Xu Zhang et al. Protein Cell. 2018 Feb.

Abstract

Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver dysfunction and a significant global health problem with substantial rise in prevalence over the last decades. It is becoming increasingly clear that NALFD is not only predominantly a hepatic manifestation of metabolic syndrome, but also involves extra-hepatic organs and regulatory pathways. Therapeutic options are limited for the treatment of NAFLD. Accordingly, a better understanding of the pathogenesis of NAFLD is critical for gaining new insight into the regulatory network of NAFLD and for identifying new targets for the prevention and treatment of NAFLD. In this review, we emphasize on the current understanding of the inter-organ crosstalk between the liver and peripheral organs that contributing to the pathogenesis of NAFLD.

Keywords: adipose tissue; gut-liver axis; hepatic lipid metabolism; hypothalamus; non-alcoholic fatty liver disease.

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Figures

Figure 1
Figure 1
The “cross-talk” between liver and peripheral organs in the pathogenesis of NAFLD. The impairment of the hypothalamic signaling pathway due to mutations (Leptin receptor and MC4R) by affecting the appetite or inflammation leads to the development of obesity and NAFLD. Dysfunction of adipose tissue in obesity, lipodystrophy or insulin resistance provides a source of excess fat and release of adipokines such as Leptin, Adiponectin, Resistin, and proinflammatory cytokines such as TNF-α and IL-6 that participated in the pathogenesis of NAFLD. In addition, emerging evidence suggests that an altered gut permeability consequently affect circulating levels of molecular such as LPS, FFA, bile acid, and to the release of pro-inflammatory cytokines by the regulation of TLR and FXR further influence the development and progression of NAFLD, recognized as effect of gut–liver axis. In the liver, the dysregulation of lipid de novo lipogenesis and imbalance of lipid influx and efflux causes lipotoxicity and may result in mitochondrial dysfunction, overproduction of ROS and ER stress as well as the consequent activation of inflammatory responses, thus influencing the risk of progression of NAFLD to NASH, as observed in obesity and insulin resistance
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