AI Article Synopsis
- Activating brown adipose tissue (BAT) is important for combating obesity and insulin resistance, and hyaluronan (HA) synthesis plays a role in this process.
- The small molecule 4-methylumbelliferone (4-MU) can inhibit HA synthesis, which leads to improved BAT thermogenesis, reduced weight gain, and better glucose control in mice on a diabetogenic diet.
- 4-MU enhances BAT function by increasing glycolysis and respiration, and could be repurposed as a potential treatment for obesity and diabetes, as it is already a clinically approved drug.
Article Abstract
Therapeutic increase of brown adipose tissue (BAT) thermogenesis is of great interest as BAT activation counteracts obesity and insulin resistance. Hyaluronan (HA) is a glycosaminoglycan, found in the extracellular matrix, which is synthesized by HA synthases (Has1/Has2/Has3) from sugar precursors and accumulates in diabetic conditions. Its synthesis can be inhibited by the small molecule 4-methylumbelliferone (4-MU). Here, we show that the inhibition of HA-synthesis by 4-MU or genetic deletion of improves BAT`s thermogenic capacity, reduces body weight gain, and improves glucose homeostasis independently from adrenergic stimulation in mice on diabetogenic diet, as shown by a magnetic resonance T2 mapping approach. Inhibition of HA synthesis increases glycolysis, BAT respiration and uncoupling protein 1 expression. In addition, we show that 4-MU increases BAT capacity without inducing chronic stimulation and propose that 4-MU, a clinically approved prescription-free drug, could be repurposed to treat obesity and diabetes.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6786893 | PMC |
| http://dx.doi.org/10.1038/s42255-019-0055-6 | DOI Listing |
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