Effect of administration of celastrol, leptin and their combination during lactation on the expression of genes related to fatty liver in high-fat diet fed rats.

Abstract

[eng] The development of obesity and complications such as fatty liver in adulthood can be influenced by nutrition in early life. Leptin and celastrol exert anti-obesity effects. Leptin, a satiating hormone, acts by transferring signals to the hypothalamus, and Celastrol, a plantderived compound, acts as leptin sensitizer (although this has only been studied in adult animals). Prior to this master work, the Nutrigenomics and Obesity (NUO) group of UIB carried out a study observing the effect of leptin and celastrol administered alone or in combination during lactation, in animals subsequently fed an isocaloric high fat (HF) diet. Surprisingly, fat deposition, was observed in the leptin+celastrol group in comparison to the control HF group. We aimed to go in-depth into liver fat accumulation in treated animals by analysing molecular markers. A bibliographic work was done to identify biomarkers of fatty liver, which could be analysed at gene expression level. Three genes were finally selected, Cyp2c19, Acly, and Dpp4. Primers were designed and their mRNA expression analysed in the rat liver samples using real time RT-PCR. The mRNA expression of Cyp2c19, gene involved in liver detoxification, was positively influenced by treatment with celastrol and leptin+celastrol. This could be attributed to the protective effect of the treatment on a HF diet. A hyperlipidic diet reduced mRNA expression of Acly, gene involved in lipogenesis, despite treatment with leptin and/or celastrol. The treatments and diet did not affect expression of Dpp4, a recognized marker of fatty liver. More research is required to understand the effect of perinatal treatments on liver fat accumulation