Apolipoprotein A5 controls fructose-induced metabolic dysregulation in mice.

Abstract

BACKGROUND AND AIMS:

Western dietary habits are partially characterized by increased uptake of fructose, which contributes to metabolic dysregulation and associated liver diseases. For example, a diet enriched with fructose drives insulin resistance and non-alcoholic fatty liver disease (NAFLD). The molecular hubs that control fructose-induced metabolic dysregulation are poorly understood. Apolipoprotein A5 (apoA5) controls triglyceride metabolism with a putative role in hepatic lipid deposition. We explored apoA5 as a rheostat for fructose-induced hepatic and metabolic disease in mammals.

METHODS AND RESULTS:

ApoA5 knock out (-/-) and wildtype (wt) mice were fed with high fructose diet or standard diet for 10 weeks. Afterwards, we conducted a metabolic characterization by insulin tolerance test as well as oral glucose tolerance test. Additionally, hepatic lipid content as well as transcription patterns of key enzymes and transcription factors in glucose and lipid metabolism were evaluated. Despite comparable body weight, insulin sensitivity was significantly improved in high fructose diet fed apoA5 (-/-) when compared to wildtype mice on the same diet. In parallel, hepatic triglyceride content was significantly lower in apoA5 (-/-) mice than in wt mice. No difference was seen between apoA5 (-/-) and wt mice on a standard diet.

CONCLUSION:

ApoA5 is involved in fructose-induced metabolic dysregulation and associated hepatic steatosis suggesting that apoA5 may be a novel target to treat metabolic diseases.

• Authors: Claudia Ress, Jochen Dobner, Kerstin Rufinatscha, Bart Staels, Maximilian Hofer, Sabrina Folie, Bernhard Radlinger, Timon E Adolph, Eduard M Rubin, Michael Roden, Herbert Tilg, Susanne Kaser
• Journal: Nutrition, metabolism, and cardiovascular diseases : NMCD (Nutr Metab Cardiovasc Dis) Vol. 31 Issue 3 Pg. 972-978 (03 10 2021) ISSN: 1590-3729 [Electronic] Netherlands
• PMID: 33549451 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2020 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.

Chemical References

• Apoa5 protein, mouse
• Apolipoprotein A-V
• Biomarkers
• Blood Glucose
• Dietary Sugars
• Fatty Acids
• Insulin
• Triglycerides
• Fructose

Topics

• Animals
• Apolipoprotein A-V (deficiency, genetics)
• Biomarkers (blood)
• Blood Glucose (metabolism)
• Dietary Sugars
• Disease Models, Animal
• Fatty Acids (blood)
• Fructose
• Insulin (blood)
• Insulin Resistance
• Liver (metabolism)
• Mice, Knockout
• Non-alcoholic Fatty Liver Disease (genetics, metabolism, prevention & control)
• Triglycerides (metabolism)
• Mice