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

Valladolid-Acebes, Ismael (author): Rolf Luft Research Center for Diabetes and Endocrinology, Karolinska Institutet, Karolinska University Hospital L1, Stockholm, Sweden

Åvall, Karin (author): Rolf Luft Research Center for Diabetes and Endocrinology, Karolinska Institutet, Karolinska University Hospital L1, Stockholm, Sweden

Recio-López, Patricia (author): Rolf Luft Research Center for Diabetes and Endocrinology, Karolinska Institutet, Karolinska University Hospital L1, Stockholm, Sweden

Bryzgalova, Galyna (author): Rolf Luft Research Center for Diabetes and Endocrinology, Karolinska Institutet, Karolinska University Hospital L1, Stockholm, Sweden

Alonso, Elena Fauste (author): Rolf Luft Research Center for Diabetes and Endocrinology, Karolinska Institutet, Karolinska University Hospital L1, Stockholm, Sweden; Facultad de Farmacia, Universidad San Pablo-CEU, CEU Universities, Madrid, Boadilla del Monte, Spain

(creator_code:org_t)

American Association for the Advancement of Science, 2021
2021
English.
In: Science Advances. - : American Association for the Advancement of Science. - 2375-2548. ; 7:11

Related links:: https://doi.org/10.1...; show more...; https://umu.diva-por... (primary) (Raw object); https://www.science....; https://urn.kb.se/re...; https://doi.org/10.1...; http://kipublication...; show less...

Abstract Subject headings

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.

By the author/editor: Valladolid-Acebe ...; Åvall, Karin; Recio-López, Pat ...; Moruzzi, Noah; Bryzgalova, Galy ...; Björnholm, Marie; show more...; Krook, Anna; Alonso, Elena Fa ...; Ericsson, Madele ...; Landfors, Fredri ...; Nilsson, Stefan ...; Berggren, Per-Ol ...; Juntti-Berggren, ...; show less...

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Endocrinology an ...

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