Lowering apolipoprotein CIII protects against high-fat diet–induced metabolic derangements

Autor: Valladolid-Acebes, Ismael, Åvall, Karin, Recio-López, Patricia, Moruzzi, Noah, Bryzgalova, Galyna, Björnholm, Marie, Krook, Anna, Alonso, Elena Fauste, Ericsson, Madelene, Landfors, Fredrik, Nilsson, Stefan K., Berggren, Per-Olof, Juntti-Berggren, Lisa
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: Science Advances
ISSN: 2375-2548
Popis: Diet-induced obesity, fatty liver, and type 2 diabetes are prevented by lowering apoCIII.
Increased levels of apolipoprotein CIII (apoCIII), a key regulator of lipid metabolism, result in obesity-related metabolic derangements. We investigated mechanistically whether lowering or preventing high-fat diet (HFD)–induced increase in apoCIII protects against the detrimental metabolic consequences. Mice, first fed HFD for 10 weeks and thereafter also given an antisense (ASO) to lower apoCIII, already showed reduced levels of apoCIII and metabolic improvements after 4 weeks, despite maintained obesity. Prolonged ASO treatment reversed the metabolic phenotype due to increased lipase activity and receptor-mediated hepatic uptake of lipids. Fatty acids were transferred to the ketogenic pathway, and ketones were used in brown adipose tissue (BAT). This resulted in no fat accumulation and preserved morphology and function of liver and BAT. If ASO treatment started simultaneously with the HFD, mice remained lean and metabolically healthy. Thus, lowering apoCIII protects against and reverses the HFD-induced metabolic phenotype by promoting physiological insulin sensitivity.
Databáze: OpenAIRE