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Research Links microRNA to Fat Cell Differentiation

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A team of German researchers this week reported on the discovery that a microRNA — miR-155 — plays a key role in the differentiation of brown and beige adipocytes, suggesting that the small, non-coding RNA could be a target for treating obesity.

The findings, which appeared in Nature Communications, come on the heels of research from another group implicating miR-155 in immune cell function (related story, this issue).

As a primary site of energy expenditure, brown adipocytes are important in thermoregulation by generating body heat, and they are particularly abundant in neonates, according to the paper. While primarily located in brown adipose tissue, brown adipocytes can also be found in white adipose tissue, which is largely used to store energy, as so-called beige cells.

The number and activity of these beige cells can be increased by cold exposure through a process known as browning, and while activation of beta-adrenergic signaling is known to be an important stimulus for browning, “not much is known about other mechanisms including microRNAs that might regulate this,” the scientists wrote in Nature Communications.

The team showed that miR-155 is enriched in brown adipose tissue, and is “highly expressed” in proliferating brown pre-adipocytes only to decline after the induction of differentiation.

The investigators also found that the miRNA and one of its targets, the adipogenic transcription factor CCAAT/enhancer-binding protein beta, form a “bistable feedback loop integrating hormonal signals that regulate proliferation or differentiation.” Inhibition of miR-155, meantime, enhances brown adipocyte differentiation and induces browning.

The researchers found that mice lacking miR-155 have increased brown adipose tissue functioning and white fat cell browning. Overexpression of the miRNA in the animals reduced brown adipose tissue mass and impaired browning.

As for what these findings may mean clinically, the team noted that miR-155 expression has been associated with adipose tissue dysfunction and obesity. And because inhibition of the miRNA by 50 percent in mice boosts recruitment of beige far cells and differentiation of brown adipose tissue, “therapeutic attempts to reduce miR-155 might be a promising approach to treat obesity,” they concluded.

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