Sequential effects of a high-fiber diet with psyllium husks on the expression levels of hepatic genes and plasma lipids.
OBJECTIVE
We studied the sequential effects of a high-fiber diet using psyllium husks on hepatic gene expression and plasma lipid levels.


METHODS
C57BL/6J mice were randomly assigned to a control diet or a high-fiber diet containing 10% psyllium husks for 3 weeks (PE-3wk) and 10 weeks (PE-10wk). Oligonucleotide microarrays were used to screen the transcriptional response at both time points. Genes encoding enzymes regulating key steps of lipid metabolism were then selected for further validation by quantitative real-time reverse transcription polymerase chain reaction and their protein expression by western blot assays.


RESULTS
Plasma cholesterol and triacylglycerol levels were reduced in both high-fiber groups. Three weeks of high-fiber feeding downregulated genes involved in lipogenesis, whereas those involved in cholesterol and bile acid synthesis were upregulated. With prolonged high-fiber feeding, genes involved in lipogenesis such as fatty acid synthase (Fasn) were then upregulated. Additional genes in cholesterol synthesis such as 3-hydroxy-3-methylglutaryl coenzyme A reductase (Hmgcr) were also upregulated. At week 3, protein expression levels of Fasn were significantly lower in the high-fiber group but increased at week 10. Protein levels of Hmgcr were significantly increased in PE-10wk mice.


CONCLUSIONS
The high-fiber diet containing psyllium husks reduced plasma total cholesterol and triacylglycerol levels. Cholesterol lowering was most likely mediated by increased bile acid synthesis. The increased transcript levels of genes related to cholesterol synthesis throughout the entire feeding period and the subsequent increased lipogenic gene transcript levels could likely suggest a regulatory mechanism to restore the lowered plasma cholesterol and triacylglycerol levels.
Chan
Mei-Yen
MY
Department of Pediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
Heng
Chew-Kiat
CK
D000214:Acyl Coenzyme A / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D002784:Cholesterol / Q000097:blood; D004043:Dietary Fiber / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D064429:Fatty Acid Synthases / Q000378:metabolism; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D050356:Lipid Metabolism; D008055:Lipids / Q000097:blood*; D050155:Lipogenesis / Q000187:drug effects*; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D051379:Mice; D008810:Mice, Inbred C57BL; D020411:Oligonucleotide Array Sequence Analysis; D011620:Psyllium / Q000008:administration & dosage / Q000494:pharmacology*; D011897:Random Allocation; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014280:Triglycerides / Q000097:blood
D000214:Acyl Coenzyme A; D004043:Dietary Fiber; D008055:Lipids; D014280:Triglycerides; C008047:3-hydroxy-3-methylglutaryl-coenzyme A; D011620:Psyllium; D002784:Cholesterol; D064429:Fatty Acid Synthases