Fat or sugar? Genes may have the deciding vote
Researchers from the University of Cambridge presented evidence in the journal Nature that a central molecular pathway may show significance in macronutrient preference in humans.
The pathway’s identification serves to establish a direct link between food preference and particular genetic variants.
By applying these insights to human gene variation, this work may explain why individuals make particular food choices, with potential implications for a deeper understanding of obesity.
The pathway in question involves the melanocortin-4 receptor (MC4R). Its disruption can lead to mice eating a lot more fat and unusually a lot less sugar.
Tests for MC4R
In a two-part study the team provided subjects with portions of chicken korma curry with varying fat levels - 20% (low), 40% (medium) and 60% (high) of the total caloric content.
Subjects were selected according to their weight with 20 lean and 20 obese subjects taking part. In addition, 14 adults with a loss of function in the MC4R gene were also selected.
Subjects were allowed to sample each of the three kormas before choosing one full portion.
Part two of the study saw the same subjects given an Eton mess - a British desert made up of strawberries, whipped cream and broken meringue.
Like the procedure for the chicken korma, subjects were allowed to sample a choice of three versions of the desert - one with low (8% of calorific content), medium (26%) and high (54%) sugar content – before selecting one for consumption.
While no overall difference in the amount of food eaten was found between the groups, subjects with the faulty MC4R gene consumed close to double the amount of high-fat korma than lean individuals and 65% more than obese individuals.
With the Eton mess, both lean and obese subjects reported a preference for the high-sugared version.
Unusually, those who had the faulty MC4R gene did not like the high-sugared version as much as the lean and obese groups. Collectively, they ate proportionally less of all three versions when compared to the other experimental groups.
“Our work shows that even if you tightly control the appearance and taste of food, our brains can detect the nutrient content. Most of the time we eat foods that are both high in fat and high in sugar,” said professor Sadaf Farooqi from the Wellcome Trust-Medical Research Council Institute of Metabolic Science at the University of Cambridge.
“By carefully testing these nutrients separately in this study, and by testing a relatively rare group of people with the defective MC4R gene, we were able to show that specific brain pathways can modulate food preference," added Farooqi, who also led the research team.
Gene influence
While a loss of function MC4R variants in humans are rare (1–5% of people with severe obesity), studies have shown the physical appearance of human MC4R deficiency is similar to mice also lacking Mc4r.
As the individual’s genetic make-up was determined beforehand, the researchers were able to directly test whether disruption of melanocortin signalling alters food preference in humans.
The team acknowledged the influence of other genes that may play a role in weight gain and eating behaviour.
Genetic variants in the protein CD36 have been linked to a preference of high-fat foods and common obesity-associated variants have been associated with dairy food choices.
Source: Nature
Published online ahead of print, doi:10.1038/ncomms13055
“Divergent effects of central melanocortin signalling on fat and sucrose preference in humans.”
Authors: Sadaf Farooqi et al.
