Hepatic fatty acid biosynthesis in KK‐A^y mice is modulated by administration of persimmon peel extract: A DNA microarray study

Abstract

ScopePreviously, we showed that the intake of a persimmon peel (PP) extract altered hepatic gene expression associated with the insulin signaling pathway and enhanced tyrosine phosphorylation of insulin receptors in nonobese type 2 diabetic Goto‐Kakizaki rats. Our objective was to evaluate the effect of fat‐soluble PP extract on obese type 2 diabetic KK‐Ay mice with insulin resistance.Methods and results KK‐Ay mice were fed a diet mixed with 0.1% of the extract for 8 weeks. The total ketone body levels in the plasma of PP extract‐fed mice were significantly lower than those in the normal diet‐fed mice. Hepatic nonesterified palmitic acid content was higher in the PP extract‐fed mice than in normal diet‐fed mice. The hepatic gene expression profiles of the treated mice indicated upregulation of fatty acid synthesis and downregulation of inflammation‐associated genes, predicting SREBP‐1c and PPARγ activation.ConclusionThese results suggest that the PP extract enhances hepatic fatty acid synthesis via SREBP‐1c and PPARγ, as well as anti‐inflammatory activity in KK‐Ay mice.

Cytochrome P450 expression-associated multiple-hit pathogenesis of non-alcoholic fatty liver disease (NAFLD) in HepG2 cells

“…ER impairment activates the unfolded protein response (UPR) and activates c-Jun N-terminal kinase (JNK), which trigger inflammation, apoptosis, and insulin resistance [13,19]. Furthermore, increased CYP2E1 and CYP4A11 expression and concomitant exposure to their substrate drugs can lead to severe cellular injury due to the over-production of toxic metabolites, such as acetone from CYP2E1 and ketone bodies from CYP4A11 [20,21]. These findings support that CYP2E1 induces fatty liver disease whether it is induced by alcohol, or not [22,23].…”