When Fat Speaks, the Body Listens

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Body fat is more than just a storage depot for our excess calories. Along with the production of hormones such as leptin, adipose tissue is also the source of microRNAs that help regulate metabolism. Lack of these miRNAs can lead to at least some of the metabolic problems often associated with obesity.

For years, researchers viewed body fat as just a passive storage depot — it was there to hold all those excess calories we consume. And while we've been aware for quite some time that too much of this excess adipose tissue can lead to problematic changes in metabolism, blood sugar control and blood pressure, many thought it was only because of changes to other types of tissues.

Over the last decade or so, however, we've seen somewhat of a paradigm shift, with adipose tissue being acknowledged as a much more active participant in metabolism. For example, it's the source of the hormone leptin (fat as an endocrine organ, anyone?) which acts on the brain to signal satiety.

More recently, researchers have been delving into the mechanisms that adipose tissue uses to affect other parts of the body. A recent report in the journal Nature investigates one possible source of such control. To describe the study we have to define a couple of terms:

microRNA (miRNA): small (19-22 nucleotides long) segments of RNA that do not code for proteins. There are many different types of miRNAs in the circulation and in different tissues, and they have various functions in the body. In general, they act to prevent translation of mRNAs and thus decrease the production of the corresponding proteins.

Dicer: an enzyme found in adipose as well as other tissues that processes miRNAs — without it miRNAs aren't produced.

Led by Dr. C. Ronald Kahn of the Joslin Diabetes Center of Harvard University, researchers bred so-called 'knockout' mice that lacked the Dicer enzyme in adipose tissue specifically. These adipose-tissue-specific Dicer knockout  (ADicerKO) mice did not produce the usual complement of miRNAs found in normal mice, showing that adipose tissue is responsible for making a large number of the circulating miRNAs. And this is important, because the presence of such miRNAs is associated with improvements in glucose tolerance and other beneficial metabolic changes.

Indeed, the ADicerKO mice exhibited a decrease in brown adipose tissue (the most metabolically active type), as well as an increase in insulin resistance. However, when both brown and white adipose tissue from normal mice was transplanted into the knockout mice, they began to produce the miRNAs, demonstrating the importance of the adipose tissue in circulating miRNA production.

In addition to their work with the mice, the investigators also compared miRNAs from patients with lipodystrophy [1] with those from control people. They found that the patients with lipodystrophy had lower levels of over 200 different miRNAs compared to the controls.

Thus, both the animal and human data suggest an important role for adipose tissue in the regulation of metabolism, and may indicate an important avenue for future research into the roles of Dicer and miRNAs in the obesity-linked derangement of blood pressure, blood glucose regulation and insulin resistance.