Metabolic disturbances caused by a high fat diet can be eliminated

Eating a high fat diet leads to an increased risk of obesity, type 2 diabetes, cardiovascular disease and fatty liver disease. A study in mice from Karolinska Institutet in Sweden shows that it is possible to eliminate the deleterious effects of a high fat diet by lowering the levels of apolipoprotein CIII (apoCIII), a key regulator of lipid metabolism. The study is published in the journal Scientific progress.

Increased levels of the apoCIII protein are linked to cardiovascular disease, insulin resistance and type 2 diabetes. Researchers from the Rolf Luft research center, Karolinska Institutet, have previously shown that apoCIII increases in the part hormonal secreting the pancreas, islets of Langerhans, in parallel with the development of insulin resistance and diabetes.

The same researchers have now studied two groups of mice fed a high-fat diet as young as 8 weeks, and a control group of mice on a normal diet. One of the high fat diet groups received so-called antisense therapy (ASO) after 10 weeks of the diet to lower apoCIII levels, and the other group had already been treated with ASO from the start, thus preventing an increase in apoCIII.

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

In the group that was treated with ASO directly from the start, the development of metabolic disturbances was prevented, and the animals had the same body composition and metabolism as the control mice on a normal diet. The mechanisms underlying the effects of apoCIII-lowering therapy involve increased enzyme activity of lipase and absorption of lipids from receptors to the liver. Fatty acids were transferred by oxidation of fatty acids in a biochemical process in the liver called the ketogenic pathway and then converted into ketones which were used for heat production in brown adipose tissue.

“Thus, we were able to demonstrate that a drop in apoCIII levels, despite the continued consumption of a high fat diet, not only protects, but also reverses the deleterious metabolic disturbances induced by fat by promoting an overall increase in insulin sensitivity, ”says Lisa Juntti -Berggren, professor in the Department of Molecular Medicine and Surgery, Karolinska Institutet, and lead author of the study.