Eating a high-fat diet increases the risk of obesity, type 2 diabetes, cardiovascular disease, and fatty liver. A study in mice from Karolinska Institutet in Sweden showed that it is possible to eliminate the harmful effects of a high-fat diet by lowering levels of lipoprotein CIII (apoCIII), a key regulator of fat metabolism. The study has been published in the journal Science Advances.
Increased levels of apoCIII are associated with cardiovascular disease, insulin resistance and type 2 diabetes. Researchers at the Rolf Luft Research Center, Karolinska Institute, have previously shown that apoCIII increases in the hormone secretion portion of the pancreas, Langerhans Islands, 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 8 weeks of age, and a control group of mice fed a normal diet. One group on a high-fat diet received so-called antiallergic therapy (ASO) after 10 weeks on the diet to reduce levels of apoCIII, and the other group had already been treated with ASO from the start thus preventing the increase of apoCIII.
“After a period of 10 weeks, all mice in Group A were obese, insulin-resistant and had steatosis in the liver. However, after the ASO treatment, with the continuation of the high-fat diet, there was a normalization of glucose metabolism, weight and liver morphology,” he said. Ismail Valladolid Acebes, Associate Professor in the Department of Molecular Medicine and Surgery, Karolinska Institute, and first author of the study says.
In the group treated with ASO directly from the start, 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. Mechanisms underlying the effects of apoCIII-lowering therapy include increased lipase activity and lipid receptor uptake into the liver. The fatty acids were transported by oxidation of the fatty acids to a biochemical process in the liver called the ketone pathway and then transformed into ketones that are used to produce heat in brown adipose tissue.
“Thus, we can demonstrate that lowering levels of apoCIII, despite consistently eating a high-fat diet, not only protects but also reverses harmful metabolic disorders induced by lipids by promoting an overall increased insulin sensitivity,” says Lisa Gunte-Bergreen, Professor in the Department of Molecular Medicine and Surgery, Karolinska Institutet, and lead author of the study.
The research was supported by the Swedish Diabetes Association, Karolinska Institute foundations and funds, Swedish Research Council, Novo Nordisk Foundation, Family Erling-Persson Foundation, Karolinska Institutet’s Strategic Diabetes Research Program, Knut and Alice Wallenberg Foundation, Stichting af Jochnick Foundation and Skandia Insurance Company Ltd. Diabetes and Wellness Foundation, Bert von Kantzow Foundation, Svenska Diabetesstiftelsen, AstraZeneca, Swedish Diabetes Association and European Research Council (ERC).
Co-author Per-Olof Berggren is the co-founder and CEO of Biocrine, a biotech company focused on apoCIII as a potential drug target in diabetes. Lisa Gunte Berggren is a consultant for the same company and has served on the advisory boards of NovoNordisk, AstraZeneca and Sanofi.
Publication: “Reducing APCIII protects against metabolic disturbances caused by a high-fat diet.” Ismail Valladolid Acebes, Karen Aval, Patricia Recio-Lopez, Noah Morozi, Galina Prizgalova, Mary Bjornholm, Anna Crook, Elena Faust Alonso, Madeleine Erickson, Frederick Landfors, Stefan Kelson, Bear-Oluftrain Berg. Science Advances, Online March 12, 2021, doi: 10.1126 / sciadv.abc2931.
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