Gene implicated in food and alcohol cravings

Behind the Headlines

Friday July 15 2011

Have we evolved to like burgers?

“Westerners are genetically programmed to drink alcohol and eat unhealthy foods, according to DNA analysis,” reported The Daily Telegraph. It said that scientists have discovered that Europeans are more likely than Asians to “have genes which urge them to gorge on fatty foods, beer and wine”.

This laboratory research investigated the role of the galanin gene in dietary preferences and mood. The galanin protein molecule coded for by the gene is produced in areas of the brain that are involved with emotions and memory. Previous studies have suggested that galanin could influence fat intake, anxiety and mood-related behaviours in rodents, while human studies have suggested an association with alcoholism and other addictive behaviours. This study investigated how the galanin gene is regulated in brain cells and, specifically, whether regulatory sequences of DNA positioned near the gene could act as a genetic switch, turning the gene on or off.

At present, very limited implications can be drawn from this research. The galanin gene and its coded protein may be involved in the regulation of food and alcohol consumption, but others could also potentially be involved, and there is no guarantee that the DNA sequences examined here are the main regulating factors for the gene.

Much more convincing evidence would need to be presented to conclude that people in the West are programmed to become obese. A healthy diet and regular exercise with moderation of alcohol intake are the best ways to maintain a healthy lifestyle, regardless of our genetics.

 

Where did the story come from?

The study was carried out by researchers from the University of Aberdeen. Funding was provided by the Tenovus Trust, Scotland, the BBSRC, the Wellcome Trust, and the Medical Research Council.

The study was published in the (peer-reviewed) scientific journal Neuropsychopharmacology.

In general, the newspapers have given a very basic interpretation of this complex scientific paper. Contrary to reports, the findings from this study do not suggest that Westerners are programmed to eat more fatty foods and consume more alcohol.

 

What kind of research was this?

This research aimed to further investigate the role of galanin (GAL) in dietary preferences and mood and, specifically, how the galanin gene is regulated (switched on and off).

GAL is a peptide made up of a chain of 30 amino acids that is produced in a number of regions in the brain. These regions include the amygdala (an area of the brain thought to be involved in processing emotion) and specific regions of the hypothalamus (an area of the brain that links the nervous system to the hormone system and plays a role in regulating body temperature, hunger, thirst and sleep).

The researchers say that studies in rodents have found that expression of the GAL protein in the paraventricular nucleus of the hypothalamus influences their fat intake and food preference. Other studies in mice have indicated that GAL may influence anxiety and mood-related behaviours. Meanwhile, recent human studies have shown that different forms of the GAL gene have been associated with elevated triglyceride (blood fat) levels, while other studies have demonstrated that variations in the GAL gene between individuals may have a role in susceptibility to alcoholism and other addictive behaviours.

Building on this previous research, the current study aimed to examine the regulatory sequences of DNA in close proximity to this GAL gene that could have a role in switching the gene on or off. The fact that other studies have noted the GAL gene to have a very precise pattern of expression in a variety of animal models, suggests that the regulatory systems vital to the genes’ functioning are likely to have also remained largely unchanged for millions of years. The current researchers aimed to look at these ‘highly conserved’ regulatory sequences.

 

What did the research involve?

The laboratory research involved cells from a type of brain cancer called neuroblastoma. These cells are often used to model neurons (brain cells) in cell culture and genetically engineered mice. The researchers used a database containing the DNA sequences of various animals to identify a sequence of DNA positioned in close proximity to the GAL gene that was highly conserved between species. They called this sequence GAL5.I.

The researchers then made genetically modified mice in which the GAL5.1 region was tagged so that they could see in which areas of the brain and spinal cord this region of DNA was active. They then used cell culture models to see how the GAL5.1 sequence affected the activity of the GAL gene.

The researchers had suggested that inappropriate regulation of the GAL gene may have a role in obesity, alcoholism and mood disorders. They used a database of human DNA sequences to look for small variations in the sequence (polymorphisms) of the GAL5.1 region. They then used rat neurons to create a cell culture model to try and determine if these polymorphisms could alter the activity of the GAL5.1 region.

 

What were the basic results?

From their initial cell culture experiments, the researchers found that GAL5.1 acted as a booster to the region of DNA responsible for switching the GAL gene on (enhanced its action).

When they looked at human GAL5.1 sequences they found that two sites in the GAL5.1 region could differ between people. In one site, some people had a “G” whereas other people had a “C”. In the second site, some people had a “G” while others had an “A”.

Every person has two copies of a gene which are called ‘alleles’. The researchers found that in 70-83% of humans both of the alleles were G ( i.e. GG). However, around 17% of the European population, 20 to 26% of the African population and about 29% of the Asian population had C and A in the two locations (i.e were CA). The researchers’ study in rat brain cells had demonstrated that the GG variant of GAL5.1 had stronger activity than the CA allele, which was 40% less active.

 

How did the researchers interpret the results?

The researchers conclude that their findings show that the DNA region called GAL5.I has a role in activating galanin expression. In their discussion, they say it would be interesting to find out whether there is a difference in the proportion of people who have each variation of the GAL5.1 and their ability to lose weight. They also discuss whether galanin may play a role in depressive diseases. They added that they want to further explore the role of GAL5.1 and its allele variants in depressive disorders.

 

Conclusion

This complex laboratory research investigates the role of the galanin gene in dietary preferences and mood, specifically looking at whether regulatory sequences of DNA positioned near the gene could act as a genetic switch, turning the gene on or off. They examined two different sequences of this ‘switch’ section of DNA, and found that one was less dominant and enhanced the switching-on of the GAL gene to a lesser extent. They also discussed their findings in the context of studies that had looked at similar regions of DNA, and had suggested a link to depressive disorders.

While the researchers hope that their developments will further our understanding of how alcoholism, obesity and depression may develop, very limited implications can be drawn from this scientific research. It cannot be concluded that galanin is the only protein regulating food and alcohol consumption or mood. Nor can it conclude that the DNA sequences that they examined are the main regulating factors for the gene.

The research does not conclude that in the West we are programmed to become obese. Lead researcher Dr Alasdair MacKenzie was interviewed by the BBC and considered that these differences could be due to evolutionary changes caused by geographical circumstances. He is quoted:

“It is possible that during the winter individuals with the weaker switch may not have survived as well in Europe as those with the stronger switch and, as a result, those in the West have evolved to favour a high-fat and alcohol-rich diet.”

However, while this carefully conducted scientific research investigates this interesting theory, the study cannot conclusively prove this one way or the other. A healthy diet and regular exercise with moderation of alcohol intake are the best ways to maintain a healthy lifestyle, regardless of our genetics.

Analysis by Bazian

Edited by NHS Choices

Links to the headlines

Westerners 'programmed for fatty foods and alcohol'. BBC News, July 15 2011

Westerners 'programmed to eat junk food'The Daily Telegraph, July 15 2011

Europeans 'evolved' to drink moreThe Independent, July 15 2011

Links to the science

Davidson S, Lear M, Shanley L et alDifferential Activity by Polymorphic Variants of a Remote Enhancer that Supports Galanin Expression in the Hypothalamus and Amygdala: Implications for Obesity, Depression and Alcoholism. Neuropsychopharmacology 2011

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