The Effect on Metabolism, Food Intake and Preferences of a Knockout Gene Variant Involved in Carbohydrate Metabolism

In this human study, effects of the SI knockout variant on metabolism, dietary habits and food preferences will be quantified. The study will be unique by being the first assessing the effect of a complete loss of SI function, which it is only feasible in Arctic populations. Differences between homozygous (HO) carriers and heterozygous (HE)/wildtype (WT) individuals are suspected to be large on a carbohydrate-rich diet and small on a traditional diet. The following hypotheses will be addressed: HO carriers metabolize carbohydrates differently than HE+WT individuals: 1. HO have a lower glycemic variability on their habitual diet than WT+HE. 2. HO have a lower glycemic variability on a starch and sucrose rich diet than WT+HE. 3. HO have a glycemic variability similar to WT+HE on a traditional diet low in carbohydrates. HO carriers have different food preferences than HE+WT individuals: 4. HO have a lower sweet taste preference compared to WT+HE. 5. HO perceive iso-intense solutions of sucrose, fructose, and glucose differently in sweet taste intensity and WT+HE will perceive them iso-intense. 6. HO consume less high-sugar-low-fat foods than WT+HE. 7. HO have similar intake and preference for high-sugar-high-fat foods as WT+HE. HO carriers have a microbiota different from HE+WT individuals: 8. Diversity and abundance of starch-fermenting bacteria is higher in HO than in WT+HE and the abundance of Parabacteroides is lower. 9. The increase in starch-fermenting bacteria as well as fecal and circulating levels of short chain fatty acids is larger for HO than in WT+HE on a starch and sucrose rich diet. 10. A diet low in carbohydrates will alter the microbiota similarly for HO and WT+HE.