Unravelling the mechanisms behind sugar sensing and regulation – and what happens when it goes wrong

By Nathan Gray contact

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Unravelling the mechanisms behind sugar sensing and regulation – and what happens when it goes wrong

Related tags: Metabolism

Genetic work in the fruit fly has revealed a complex sugar sensing regulatory network, which when dysregulated leads to severely disturbed energy metabolism, say researchers.

The new research, published in Cell Reports​, analysed the genetics of the fruit fly – identifying a sugar sensing regulatory network which is composed of several genes, and may be implicated in metabolic conditions like insulin sensitivity and diabetes.

Led by Ville Hietakangas from the University of Helsinki, the team noted that changes in nutrient intake require adjustments of the energy metabolism, which is done through sophisticated monitoring mechanisms that are collectively referred to as nutrient sensing pathways. These nutrient sensing pathways react to changes in the levels of major energy sources like sugars, lipids and amino acids, and control the metabolism in order to maintain an internal balance.

As a result of research on the fruit fly Drosophila melanogaster, the research group has now discovered that a sugar sensor known as Mondo-Mlx is a transcription factor that controls the activity of other genes and acts as a master regulator of a large sugar-responsive regulatory network.

"The Mondo-Mlx sugar sensor regulates the majority of sugar responsive genes in several tissues. In addition to the control of metabolic genes, the Mondo-Mlx sugar sensor also controls other regulatory genes, including other transcription factors such as Sugarbabe, as well as hormones involved in metabolic regulation,"​ said Hietakangas.

According to the team, deregulation of this sugar sensing network leads to severely disturbed energy metabolism, while the Hietakangas group has already shown that loss of the Mondo-Mlx function leads to severe sugar intolerance.

"Larvae lacking the mlx -gene die as larvae if they are fed food containing sugar. Similar sugar intolerance has been observed in mutant mice. This suggests that the Mondo-Mlx function has been well conserved during evolution, which is a strong indication about the importance of its function,"​ said the lead researcher. 

Metabolic implications

The authors added that the new insights gained from the study may also benefit research into human metabolic diseases like diabetes.

Indeed, other research has suggested that that many of the Mondo-Mlx target genes are associated with blood triglyceride levels in humans, said the team – noting that elevated blood triglyceride levels are known to increase the risk of cardiovascular diseases.

Source: Cell Reports
Published online, Open Access, doi: 10.1016/j.celrep.2015.08.081
“Mondo-Mlx Mediates Organismal Sugar Sensing through the Gli-Similar Transcription Factor Sugarbabe”
Authors: Jaakko Mattila, et al

Related topics: Science

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