The inverse association between ANGPTL8 and PI3K-mTOR- PPARγ expressions in adipose tissue of high-fructose- fed rats: The modulatory effect of kefir

Background and Aims: The dietary high-fructose intake might be a risk factor for several metabolic diseases. Kefir, a fermented milk product, has been proposed to have beneficial health effects. In this study, we aimed to investigate the effects of fructose consumption and kefir supplementation on the lipogenesis-related genes including angiopoietin-like protein 8 (angptl8), phosphoinositide 3-kinase (pi3k), mammalian target of rapamycin (mtor), and peroxisome proliferator-activated receptor γ (pparγ) as well as inflammatory factors in the adipose tissue to provide new mechanistic insights into lipogenesis. Methods: Fructose was given to the rats as a 20% solution in drinking water for 15 weeks. Kefir was administered by gastric gavage once a day during the final six weeks. Results: There was an upregulation of angptl8 mRNA expression in adipose tissue of rats given fructose. However, expressions of pi3k, mtor, and pparγ mRNAs were impaired in the adipose tissue. The increased interleukin (IL)-1β levels, but decreased IL-10, were also measured. There was no change in expressions of sirtuin1 (sirt1) and nuclear factor erythroid 2-related factor 2 (nrf2). Kefir supplementation suppressed expression of angptl8, but increased pi3k and mtor in the adipose tissue of high-fructose-fed rats. Conclusion: Activation of gene expression of angptl8, together with the suppression of pi3k, mtor, and pparγ, showed that there was an inverse association between these lipogenic genes in the adipose tissue of rats fed with high-fructose. Kefir supplementation has modulatory effects on fructose-induced changes except for pparγ expression. These findings showed that dietary fructose and kefir might reciprocally affect the lipogenesis-related genes in the adipose tissue.