Molecular pathways involved in the improvement of non-alcoholic fatty liver disease

Gilberto Paz-Filho, Claudio Mastronardi, Brian Parker, Ainy Khan, Antonio Inserra, Klaus Matthaei, Monika Ehrhart-Bornstein, Stefan Bornstein, Ma-Li Wong, Julio Licinio

    Research output: Contribution to journalArticlepeer-review

    11 Citations (Scopus)

    Abstract

    Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis are components of the metabolic syndrome. Serum leptin levels are elevated in obesity, but the role of leptin in the pathophysiology of the liver involvement is still unclear. To identify the effects and mechanisms by which leptin influences the pathogenesis of NAFLD, we performed epididymal white adipose tissue (eWAT) transplantation from congenic wild-type mice into the subcutaneous dorsal area of Lepob/ob recipient mice and compared the results with those of the Lepob/ob sham-operated mice. The mice were followed for 102-216 days. During killing, the transplanted mice had significantly lost body weight and exhibited significantly higher leptin levels, improved glucose tolerance, and lower liver injury scores than the sham-operated mice. Liver microarray analysis showed that novel pathways related to GA-binding protein (GABP) transcription factor targets, pheromone binding, and olfactory signaling were differentially expressed in the transplanted mice. Our data also replicate pathways known to be involved in NAFLD, such as those involved in the regulation of microRNAs, lipid, glucose, and glutathione metabolism, peroxisome proliferator-activated receptor signaling, cellular regulation, carboxylic acid processes, iron, heme, and tetrapyrrole binding, immunity and inflammation, insulin signaling, cytochrome P450 function, and cancer. Conclusion: wild-type eWAT transplantation into Lepob/ob mice led to improvements in metabolism, body weight, and liver injury, possibly attributed to the production of leptin by the transplanted eWAT. These improvements were accompanied by the differential expression of novel pathways. The causal relationship between GABP downregulation and NAFLD improvement remains to be determined.

    Original languageEnglish
    Pages (from-to)167-179
    Number of pages13
    JournalJournal of Molecular Endocrinology
    Volume51
    Issue number1
    DOIs
    Publication statusPublished - 2013

    Keywords

    • Adipose tissue
    • Leptin
    • Liver
    • Microarray

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