High adiponectin levels are present in the cord blood. Cord plasma adiponectin and leptin levels are positively correlated with birthweight and adiposity. This suggests that adiponectin may be involved in regulating fetal growth.

No abstract

Protective effects of adiponectin (APN; an adipocytokine) were shown against various oxidative challenges; however, its therapeutic implications and the mechanisms underlying hepatic iron overload remain unclear. Herein, we show that the deleterious effects of iron dextran on liver function and iron deposition were significantly reversed by adiponectin gene therapy, which was accompanied by AMP-activated protein kinase (AMPK) phosphorylation and heme oxygenase (HO)-1 induction. Furthermore, AMPK-mediated peroxisome proliferator-activated receptor-␣ (PPAR␣) activation by APN was ascribable to HO-1 induction. Additionally, we revealed direct transcriptional regulation of HO-1 by the binding of PPAR␣ to a PPAR-responsive element (PPRE) by various experimental assessments. Interestingly, overexpression of HO-1 in hepatocytes mimicked the protective effect of APN in attenuating iron-mediated injury, whereas it was abolished by SnPP and small interfering HO-1. Furthermore, bilirubin, the end-product of the HO-1 reaction, but not CO, protected hepatocytes from iron dextran-mediated caspase activation. Herein, we demonstrate a novel functional PPRE in the promoter regions of HO-1, and APN-mediated HO-1 induction elicited an antiapoptotic effect and a decrease in iron deposition in hepatocytes subjected to iron challenge.

No abstract

Oxidative stress results in structural and functional abnormalities in the liver and is thought to be a crucial factor in liver diseases. The aim of this study was to investigate the cytoprotective and antioxidant effects of caffeic acid (CA) derivatives on tert-butyl hydroperoxide (t-BHP)-induced oxidative stress in HepG2 cells. Nine CA derivatives were synthesized, including N-phenylethyl caffeamide (PECA), N-(3-florophen)methyl caffeamide (FMCA), N-(4-methoxy-phen)methyl caffeamide (MPMCA), N-heptyl caffeamide (HCA), N-octyl caffeamide (OCA), octyl caffeate (CAOE), phenpropyl caffeate (CAPPE), phenethyl caffeate (CAPE), and phenmethyl caffeate (CAPME). The results showed that CA and its derivatives significantly inhibited t-BHP-induced cell death of HepG2 cells. The rank order of potency of the CA derivatives for cytoprotection was CAOE > HCA > OCA > FMCA > CAPPE > CAPME > CAPE > PECA > MPMCA > CA. Their cytoprotective activity was associated with lipophilicity. The antioxidant effect of these compounds was supported by the reduction in the levels of thiobarbituric acid reactive substrates, a biomarker of lipid peroxidation, in HepG2 cells. Pre-treatment of CA derivatives significantly prevented the depletion of glutathione, the most important water-soluble antioxidant in hepatocytes. Pre-treatment of CA derivatives before t-BHP exposure maintained mitochondrial oxygen consumption rate and ATP content in the injured HepG2 cells. CA derivatives except OCA and HCA significantly suppressed t-BHP-induced hypoxia-inducible factor-1α (HIF-1α) protein level. In addition, all of these CA derivatives markedly increased the nuclear factor erythroid 2-related factor 2 (Nrf2) accumulation in the nucleus, indicating that their cytoprotection may be mediated by the activation of Nrf2. Our results suggest that CA derivatives might be a hepatoprotective agent against oxidative stress.