Metabolic breakdowns caused by a high-fat diet can be eliminated

Eating a high-fat diet increases the risk of obesity, type 2 diabetes, cardiovascular disease and fatty liver. A mouse study at the Karolinska Institutet in Sweden shows that it is possible to eliminate the deleterious effects of a high-fat diet by reducing levels of apolipoprotein CIII (apoCIII), a key regulator of lipid metabolism. The study is published in the journal Advances in Science.

Increased levels of the apoCIII protein are related to cardiovascular disease, insulin resistance and type 2 diabetes. Researchers at the Rolf Luft Research Center, Karolinska Institutet, previously demonstrated that apoCIII increases in the secretory part of the pancreas hormones, the islets of Langerhans, in parallel with the development of insulin resistance and diabetes.

The same researchers have now studied two groups of mice that have been fed a high-fat diet since the age of 8 weeks, and a control group of mice with a normal diet. One of the groups on a high-fat diet received so-called antisense treatment (ASO) after 10 weeks on the diet to decrease apoCIII levels, and the other group had already been treated with ASO from the beginning, thereby preventing an increase in apoCIII.

“After a period of 10 weeks, all mice in the first group were obese, insulin resistant and had hepatic steatosis. However, after treatment with ASO, still on a high-fat diet, there was a normalization of glucose metabolism, weight and liver morphology “, says Ismael Valladolid-Acebes, assistant professor in the Department of Molecular Medicine and Surgery at the Karolinska Institutet and first author of the study.

In the group that was treated with ASO directly from the beginning, the development of metabolic breakdowns was prevented, and the animals had the same body composition and metabolism as the control rats on a normal diet. The mechanisms underlying the effects of the apoCIII-reducing treatment involve increased activity of the lipase enzyme and receptor-mediated lipid uptake into the liver. Fatty acids were transferred by oxidation of fatty acids to the biochemical process in the liver, called the ketogenic pathway, and then converted into ketones that were used for the production of heat in the brown adipose tissue.

“Thus, we can demonstrate that the reduction of apoCIII levels, despite the continuous intake of a high-fat diet, not only protects, but also reverses the harmful metabolic disorders induced by fat, promoting an overall increase in insulin sensitivity,” he said. Lisa Juntti. -Berggren, professor in the Department of Molecular Medicine and Surgery, Karolinska Institutet, and senior author of the study.