Tuesday, May 24, 2011

More on microRNAs - a nutrition connection

The landscape at the intersection of microRNA (miR) expression and diet is sparse. This is even more so concerning the consequence of bioactive food components in affecting the physical aspects of the miR-mRNA interaction.

Nonetheless, evidence has been reported to suggest that miRs are key metabolic regulators. In adipose of mice, expression of miRs was shown to be sensitive to conjugated linoleic acid in the diet. In rats fed a diet of corn oil/fish oil with pectin/cellulose and in which colonic tumors were induced, a number of miRs, including miR-16, miR-19b, miR-21, miR-26b, miR-27b, miR-93 and miR-203, exhibited altered expression and were linked to oncogenic signaling pathways. Also in rats, downregulation in the liver of three miRs (miR-122, miR-451 and miR-27) and upregulation of miR-200a, miR-200b and miR-429 was noted after feeding of either a high-fat or high-fructose diet with consequences of diet-induced nonalcoholic fatty liver disease.

In mice, pregnant and lactating dams fed a high-fat diet displayed reduced expression of miR-26a, miR-122, miR-192, miR-194, miR-709 and the let-7 family with a common predicted target of methyl-CpG binding protein 2 (Mecp2).

A comparison of miR expression profiles in subcutaneous adipose of women highlighted eleven miRNAs as significantly deregulated in obese subjects with and without type 2 diabetes. Many of the same miRs also showed significant deregulation during adipocyte differentiation. The role of diet in regulating miR expression in prostate cancer has been reviewed. MiR-33, encoded in an intron of SERBF1/SREBF2, cooperatively regulates cholesterol homeostasis via targeting of ABCA1 and NPC1. The FXR/SHP signaling cascade regulates miR-34a and its target SIRT1, which likely functions as either a regulator of epigenetic gene silencing or an intracellular regulatory protein with mono-ADP-ribosyltransferase activity.

Using a mouse diet-induced obesity model, it was shown that hepatic expression of miR-107 decreases while its target FASN, encoding fatty acid synthase, increases.

In summary, there is a growing body of evidence to strongly implicate microRNAs as having significant functions in regulating the metabolic-based response of a number of cell types.