Thursday, August 11, 2022

Fat Tissue miRNAs

Here is an article from several years ago that should raise some eyebrows, and we'll have to keep track of further developments in this field.  Abstract:

Adipose tissue is a major site of energy storage and has a role in the regulation of metabolism through the release of adipokines. Here we show that mice with an adipose-tissue-specific knockout of the microRNA (miRNA)-processing enzyme Dicer (ADicerKO), as well as humans with lipodystrophy, exhibit a substantial decrease in levels of circulating exosomal miRNAs. Transplantation of both white and brown adipose tissue-brown especially-into ADicerKO mice restores the level of numerous circulating miRNAs that are associated with an improvement in glucose tolerance and a reduction in hepatic Fgf21 mRNA and circulating FGF21. This gene regulation can be mimicked by the administration of normal, but not ADicerKO, serum exosomes. Expression of a human-specific miRNA in the brown adipose tissue of one mouse in vivo can also regulate its 3' UTR reporter in the liver of another mouse through serum exosomal transfer. Thus, adipose tissue constitutes an important source of circulating exosomal miRNAs, which can regulate gene expression in distant tissues and thereby serve as a previously undescribed form of adipokine.

So we have known for a long time that fat (adipose) tissue can release macromolecular factors (adipokines) that can affect metabolism of other tissues.  These adipokines may mediate some  of the negative health effects of obesity including an increased risk for cancer. MicroRNAs (miRNAs) are small RNA molecules that affect gene expression by binding to target mRNA and are this crucially important to both normal function and to disease.  Initially, it was thought that the miRNAs operated within the cell producing them, but later it was learned that miRNAs can be released by one cell to affect others (exosomal miRNAs).  This paper shows that fat tissue is an important source of such circulating miRNAs, demonstrating another mechanism by which fat tissue can affect metabolism of other parts of the body, contributing to human disease.

The harmful effects of overweight/obesity keep on growing.