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.

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The mechanism of iron release from ferritin in vivo is still unclear even though it represents a key step of the metabolism of iron in vivo. Here, both interaction intensity and binding stability between epigallocatechin gallate (EGCG) from tea and liver ferritin of Dasyatis akajei (DALF) were investigated using UV-visible, fluorescence and circular dichroism (CD) spectrometry, respectively. The results indicated that EGCG could reduce the iron within the ferritin shell directly in the absence of chemical reducers such as Na(2)S(2)O(4), but this process was strictly pH-dependent, and the rate of iron release is faster at low pH than at high pH. The kinetic study of iron release showed that this process fitted the law of zero order reaction, which differed from that of first order reaction by various chemical reducers such as Vitamin C. In addition, Both fluorescence and CD spectrometry were further used to study the reduction mechanism of iron release in vitro, showing that there was a slight conformation change of the ferritin shell during EGCG reduction because of a complex formation of DALF-EGCG. It appears that chemical reducers with large molecular sizes reduce the iron across the protein shell by the way of an electron transfer pathway (ETP). A novel pathway for iron release from DALF with EGCG reduction is suggested to explain for a reductive route of iron metabolism by biological reducers in vivo.

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Background and Purpose Dopamine agonists targeting D2 receptor have been used for decades in treating pituitary adenomas. There has been little clear evidence implicating the canonical G protein signalling as the mechanism by which D2 receptor suppresses the growth of pituitary tumours. We hypothesize that β‐arrestin2‐dependent signalling is the molecular mechanism dictating D2 receptor inhibitory effects on pituitary tumour growth. Experimental Approach The involvement of G protein and β‐arrestin2 in bromocriptine‐mediated growth suppression in rat MMQ and GH3 tumour cells was assessed. The anti‐growth effect of a β‐arrestin2‐biased agonist, UNC9994, was tested in cultured cells, tumour‐bearing nude mice and primary cultured human pituitary adenomas. The effect of G protein signalling on tumour growth was also analysed by using a G protein‐biased agonist, MLS1547, and a Gβγ inhibitor, gallein, in vitro. Key Results β‐arrestin2 signalling but not G protein pathways mediated the suppressive effect of bromocriptine on pituitary tumour growth. UNC9994 inhibited pituitary tumour cell growth in vitro and in vivo. The suppressive function of UNC9994 was obtained by inducing intracellular reactive oxygen species generation through downregulating mitochondrial complex I subunit NDUFA1. The effects of Gαi/o signalling and Gβγ signalling via D2 receptor on pituitary tumour growth were cell‐type‐dependent. Conclusion and Implications Given the very low expression of Gαi/o proteins in pituitary tumours and the complexity of the responses of pituitary tumours to G protein signalling pathways, our study reveals D2 receptor β‐arrestin2‐biased ligand may be a more promising choice to treat pituitary tumours with improved therapeutic selectivity.