The Putative Antilipogenic Role of NRG4 and ERBB4: First Expression Study on Human Liver Samples.

BACKGROUND

Epidermal growth factor receptor 4 (ERBB4) and neuregulin 4 (NRG4) have been shown to reduce steatosis and prevent the development of non-alcoholic steatohepatitis in mouse models, but little to nothing is known about their role in non-alcoholic fatty liver disease (NAFLD) in humans. This study is the first to investigate the expression of and mRNAs and their role in lipid metabolism in the livers of individuals with obesity, type 2 diabetes and biopsy-proven NAFLD.

METHODS

Liver biospecimens were obtained intraoperatively from 80 individuals. Quantitative reverse transcription polymerase chain reaction was used to measure the expression levels of mRNAs and , as well as key lipogenesis genes in the liver tissue of the donors. Histological analysis was conducted on liver biopsies from 36 subjects, and the levels of the examined transcripts were compared with the stage of NAFLD.

RESULTS

In individuals with elevated body mass index (BMI), and levels decreased, while levels increased. A strong negative correlation was observed between and levels. No deregulation of the analyzed transcripts was detected in NAFLD.

CONCLUSIONS

The study demonstrates a decrease in and mRNA expression in the livers of subjects with high BMI but not in those with NAFLD. The correlation of the studied transcripts with major lipogenesis genes was assessed, and on this basis a putative scheme for NRG4-mediated suppression of hepatic lipogenesis was hypothesised, offering new research vectors in this field.