Lowering apolipoprotein CIII levels can prevent deleterious effects of a high-fat diet

Consumption of a diet with high-fat levels increases the risk of fatty liver, obesity, cardiovascular diseases, and type 2 diabetes.

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Researchers from Karolinska Institutet have performed a study in mice that demonstrates the deleterious effects of a high-fat diet can be avoided by reducing the levels of apolipoprotein CIII (apoCIII), the main regulator of lipid metabolism. The research was published recently in the Science Advances journal.

Elevated levels of apoCIII protein are associated with insulin resistance, cardiovascular diseases, and type 2 diabetes. Scientists from the Rolf Luft Research Center, Karolinska Institutet, have already demonstrated that apoCIII increases in the hormone-secreting part of the pancreas, the islets of Langerhans, corresponding to the development of insulin resistance and diabetes.

The same team has now investigated two groups of mice fed with a high-fat diet from the age of 8 weeks and a control group of mice fed with a normal diet. One part of the group on the high-fat diet was administered what is called the antisense (ASO) treatment following 10 weeks into the diet to bring down the apoCIII levels, and the other part had already been treated using ASO from the start, thus inhibiting an increase in apoCIII.

Normalization of weight

After a period of 10 weeks, all of the mice in the first group were obese, insulin resistant and had liver steatosis. However, after ASO treatment, still being on the high-fat diet, there was a normalisation of glucose metabolism, weight and liver morphology.”

Ismael Valladolid-Acebes, Study First Author and Assistant Professor, Department of Molecular Medicine and Surgery, Karolinska Institutet

The development of metabolic derangements was inhibited in the group treated with ASO directly from start, and the animals exhibited the same metabolism and body composition as the control mice fed with a normal diet.

The mechanisms behind the effects of the apoCIII-reducing treatment are elevated lipase enzyme activity and receptor-induced uptake of lipids to the liver. Fatty acid oxidation enabled the transfer of fatty acids to the biochemical process in the liver known as the ketogenic pathway and then modified to ketones used for heat production in brown adipose tissue.

Reverses metabolic derangements

Thus, we could demonstrate that a lowering of apoCIII levels, despite ongoing intake of a high-fat diet, not only protects against, but also reverses the deleterious fat-induced metabolic derangements by promoting an overall increased insulin sensitivity.”

Lisa Juntti-Berggren, Study Senior Author and Professor, Department of Molecular Medicine and Surgery, Karolinska Institutet