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Purposes: Hepatic lipid overloading induces lipotoxicity which can cause hepatocyte damage, fibrosis, and eventually progress to cirrhosis, which is associated with nonalcoholic fatty liver disease. Adiponectin receptors play important roles in regulating lipid metabolism. In this study, we used a lentivirus system to overexpress the adiponectin receptor 1 (AdipoR1) in HepG2 cells to define the role of adiponectin and its receptor 1 in the development of fatty liver syndrome. Methods and results: Exposure of human hepatocytes, HepG2 cells, to palmitate (0.2 or 0.4 mM) for 16 h resulted in elevated apoptosis, whereas AdipoR1 decreased the palmitate-induced apoptosis. Transgene AdipoR1 increased the expression of FATP2, acyl-coA oxidase, and carnitine palmitoyltransferase I in palmitate-treated HepG2 cells. The transcript level of acetyl-CoA carboxylase and fatty acid synthase was upregulated by palmitate treatment, while AdipoR1 reversed the effect induced by palmitate. AdipoR1 increased the gene expression of cytochrome C oxidase, peroxisome proliferator-activated receptor α, and decreased the gene expression of PGC1α and AMPKα in HepG2 cells under palmitate treatment. Palmitate suppressed ATP production, while transgene AdipoR1 reversed the decreased ATP production by palmitate. Transgene AdipoR1 enhanced AKT phosphorylation in HepG2 cells both with and without palmitate treatment. When PI3 kinase inhibitor was applied, the protective effect of AdipoR1 was absent, such that palmitate again decreased ATP production while also reducing cell viability. Conclusion: AdipoR1 enhances fatty acid metabolism and cell viability in palmitate-treated HepG2 cells partially by activating AKT signaling. Therefore, AdipoR1 has therapeutic potential in the treatment of nonalcoholic fatty liver disease. [ABSTRACT FROM AUTHOR]

Our previous study showed that the recombinant ATPase encoded by the A32L gene of orf virus displayed ATP hydrolysis activity as predicted from its amino acids sequence. This viral ATPase contains four known functional motifs (motifs I-IV) and a novel AYDG motif; they are essential for ATP hydrolysis reaction by binding ATP and magnesium ions. The motifs I and II correspond with the Walker A and B motifs of the typical ATPase, respectively. To examine the biochemical roles of these five conserved motifs, recombinant ATPases of five deletion mutants derived from the Taiping strain were expressed and purified. Their ATPase functions were assayed and compared with those of two wild type strains, Taiping and Nantou isolated in Taiwan. Our results showed that deletions at motifs I-III or IV exhibited lower activity than that of the wild type. Interestingly, deletion of AYDG motif decreased the ATPase activity more significantly than those of motifs I-IV deletions. Divalent ions such as magnesium and calcium were essential for ATPase activity. Moreover, our recombinant proteins of orf virus also demonstrated GTPase activity, though weaker than the original ATPase activity., (Copyright © 2011 Elsevier Inc. All rights reserved.)