Dietary Sugars Alter Hepatic Fatty Acid Oxidation via Transcriptional and Post-translational Modifications of Mitochondrial Proteins

Dietary sugars, fructose and glucose, promote hepatic de novo lipogenesis and modify the effects of a high-fat diet (HFD) on the development of insulin resistance. Here, we show that fructose and glucose supplementation of an HFD exert divergent effects on hepatic mitochondrial function and fatty ac...

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Detalhes bibliográficos
Autores: Softic, Samir, Meyer, Jesse G., Wang, Guo-Xiao, Gupta, Manoj K, Batista, Thiago M, Lauritzen, Hans P M M, Fujisaka, Shiho, Serra i Cucurull, Dolors, Herrero Rodríguez, Laura, Willoughby, Jennifer, Fitzgerald, Kevin, Ilkayeva, Olga, Newgard, Christopher B, Gibson, Bradford W, Schilling, Birgit, Cohen, David E, Kahn, C. Ronald
Formato: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2019
País:España
Recursos:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/167638
Acesso em linha:https://hdl.handle.net/2445/167638
Access Level:acceso abierto
Palavra-chave:Malalties del fetge
Obesitat
Fructosa
Glucosa
Liver diseases
Obesity
Fructose
Glucose
Descrição
Resumo:Dietary sugars, fructose and glucose, promote hepatic de novo lipogenesis and modify the effects of a high-fat diet (HFD) on the development of insulin resistance. Here, we show that fructose and glucose supplementation of an HFD exert divergent effects on hepatic mitochondrial function and fatty acid oxidation. This is mediated via three different nodes of regulation, including differential effects on malonyl-CoA levels, effects on mitochondrial size/protein abundance, and acetylation of mitochondrial proteins. HFD- and HFD plus fructose-fed mice have decreased CTP1a activity, the rate-limiting enzyme of fatty acid oxidation, whereas knockdown of fructose metabolism increases CPT1a and its acylcarnitine products. Furthermore, fructose-supplemented HFD leads to increased acetylation of ACADL and CPT1a, which is associated with decreased fat metabolism. In summary, dietary fructose, but not glucose, supplementation of HFD impairs mitochondrial size, function, and protein acetylation, resulting in decreased fatty acid oxidation and development of metabolic dysregulation.

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