Metabolic disorders caused by a high fat diet may be eliminated

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

Elevated levels of the protein apoCIII are associated with cardiovascular disease, insulin resistance and type 2 diabetes. Researchers at the Rolf Luft Research Center, Karolinska Institutet, have previously shown that apoCIII increases in the hormone-secreting part of the pancreas, the islets of Langerhans, in parallel with the development of insulin resistance and diabetes.

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

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

In the group treated directly with ASO from the outset, the development of metabolic disorders 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 treatment involve increased lipase enzyme activity and receptor-mediated uptake of lipids into the liver. Fatty acids are transferred by oxidation of fatty acids to the biochemical process in the liver, called the ketogenic pathway, and then converted to ketones used for heat production in brown adipose tissue.

“We can therefore demonstrate that a reduction in apoCIII levels, despite continuous intake of a fatty fat, not only protects against harmful fat-induced metabolic disorders, but also reverses it by promoting an overall increased insulin sensitivity,” says Lisa Juntti -Berggren , professor at the Department of Molecular Medicine and Surgery, Karolinska Institutet, and senior author of the study.