Genetic mutation prevents weight gain on high-sugar diet
28 Oct 2014 by Evoluted New Media
A team of researchers from the University of Southern California have found a way to suppress the obesity that accompanies a high-sugar diet by regulation of a particular gene.
The team, led by Assistant Professor Sean Curran of the USC School of Gerontology, have focused their study on the worm Caenorhabditis elegans and they have discovered that certain genetic mutations – those with a hyperactive SKN-1 gene – could be fed incredibly high-sugar diets without gaining any weight, while regular C. elegans significantly increased in size.
“The high-sugar diet that the bacteria ate was the equivalent of a human eating the Western diet,” said Curran, referring to the common diet eaten in the Western World, characterised by fast foods such as burgers and fries, sweets and sugary drinks.
The study - published in Nature Communications - has so far been limited to C. elegans, although the genetic pathway studied is also found in humans, where it is called Nrf2. This suggests that the findings can be translated and applied to human studies.
The Nrf2 protein is a “transcription factor” that binds to a specific sequence of DNA to regulate cellular responses to oxidative damage. It also plays an important role in metabolic homeostasis. Pharmaceutical companies have already worked to develop small-molecule drugs that target Nrf2, to increase its production of anti-oxidants and slow ageing. A similar pill could be developed to tackle obesity.
“Though the promise of a pill to help control your body’s response to food is enticing, it is not without risk,” Curran conceded. Increased expression of Nrf2 has been linked to worsening insulin resistance and increased risk of certain aggressive cancers. However: “Previous work has enhanced Nrf2 by inhibiting its negative regulator Keap1,” said Curran. “Our study demonstrates an alternative means of activating this pathway.”
“Perhaps it is a matter of timing and location,” He added, “If we can acutely activate Nrf2 in specific tissues when needed then maybe we can take advantage of its potential benefits.”
Many high-sugar foods also contain large amounts of fat; hence the team’s next study will integrate diets with altered lipid content.
SKN-1 and Nrf2 couples proline catabolism with lipid metabolism during nutrient deprivation
By Rebecca Dey
