Experts have been warning for years that foods loaded with high levels of fructose and other processed carbohydrates are making us fatter. We have now uncovered the genetic basis for why this is so, a gene in the liver, called SCD-1, is what causes mice to gain weight on a diet laden with carbohydrates. The gene encodes the enzyme SCD, whose job is to synthesize fatty acids that are a major component of fat. When we fed a starch- and sugar-rich diet to mice lacking SCD-1 in the liver, the extra carbohydrates were broken down rather than being converted into fat and stored – keeping the mice skinny. Meanwhile, control mice with normal gene activity grew plump on the same food.

High-carbohydrate diets have become exceedingly common not only in western nations but also in the developing world, as sugary ingredients like high-fructose corn syrup have crept into all sorts of processed foods, including soft drinks, baked goods, condiments – even supposedly healthy items like low-fat, fruit yogurt. What our team has now demonstrated is how those diets can act directly on a gene to boost fat synthesis and storage.

This current study builds on previous collaborative work, in which we created mice that lacked SCD-1 everywhere in the body, including the liver, muscle, brain, pancreas and adipose tissue. No matter how much they ate, the mice didn’t gain weight on either a high-fat or a high-carbohydrate diet. The findings also highlight the central role of the enzyme and its main product, a fatty acid known as oleic acid, in overall carbohydrate metabolism. For example, mice lacking SCD could no longer make glucose – the sugar burned by cells for energy – leading to abnormally low blood sugar levels, or hypoglycemia. They also weren’t able to make glycogen, a short-term storage form of glucose.