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Impaired Very-Low-Density Lipoprotein catabolism links hypoglycemia to hypertriglyceridemia in Glycogen Storage Disease type Ia.
Hoogerland, Joanne A; Peeks, Fabian; Hijmans, Brenda S; Wolters, Justina C; Kooijman, Sander; Bos, Trijnie; Bleeker, Aycha; van Dijk, Theo H; Wolters, Henk; Gerding, Albert; van Eunen, Karen; Havinga, Rick; Pronk, Amanda C M; Rensen, Patrick C N; Mithieux, Gilles; Rajas, Fabienne; Kuipers, Folkert; Reijngoud, Dirk-Jan; Derks, Terry G J; Oosterveer, Maaike H.
Afiliação
  • Hoogerland JA; Department of Pediatrics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
  • Peeks F; Department of Pediatrics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
  • Hijmans BS; Department of Metabolic Diseases, Beatrix Children's Hospital, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
  • Wolters JC; Department of Pediatrics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
  • Kooijman S; Department of Pediatrics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
  • Bos T; Department of Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, The Netherlands.
  • Bleeker A; Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands.
  • van Dijk TH; Department of Pediatrics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
  • Wolters H; Department of Pediatrics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
  • Gerding A; Department of Laboratory Medicine, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
  • van Eunen K; Department of Pediatrics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
  • Havinga R; Department of Pediatrics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
  • Pronk ACM; Department of Laboratory Medicine, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
  • Rensen PCN; Department of Pediatrics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
  • Mithieux G; Department of Pediatrics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
  • Rajas F; Department of Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, The Netherlands.
  • Kuipers F; Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands.
  • Reijngoud DJ; Department of Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, The Netherlands.
  • Derks TGJ; Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands.
  • Oosterveer MH; Institut National de la Santé et de la Recherche Médicale, U1213, Lyon, France.
J Inherit Metab Dis ; 44(4): 879-892, 2021 07.
Article em En | MEDLINE | ID: mdl-33739445
ABSTRACT
Prevention of hypertriglyceridemia is one of the biomedical targets in Glycogen Storage Disease type Ia (GSD Ia) patients, yet it is unclear how hypoglycemia links to plasma triglyceride (TG) levels. We analyzed whole-body TG metabolism in normoglycemic (fed) and hypoglycemic (fasted) hepatocyte-specific glucose-6-phosphatase deficient (L-G6pc-/- ) mice. De novo fatty acid synthesis contributed substantially to hepatic TG accumulation in normoglycemic L-G6pc-/- mice. In hypoglycemic conditions, enhanced adipose tissue lipolysis was the main driver of liver steatosis, supported by elevated free fatty acid concentrations in GSD Ia mice and GSD Ia patients. Plasma very-low-density lipoprotein (VLDL) levels were increased in GSD Ia patients and in normoglycemic L-G6pc-/- mice, and further elevated in hypoglycemic L-G6pc-/- mice. VLDL-TG secretion rates were doubled in normo- and hypoglycemic L-G6pc-/- mice, while VLDL-TG catabolism was selectively inhibited in hypoglycemic L-G6pc-/- mice. In conclusion, fasting-induced hypoglycemia in L-G6pc-/- mice promotes adipose tissue lipolysis and arrests VLDL catabolism. This mechanism likely contributes to aggravated liver steatosis and dyslipidemia in GSD Ia patients with poor glycemic control and may explain clinical heterogeneity in hypertriglyceridemia between GSD Ia patients.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Triglicerídeos / Hipertrigliceridemia / Doença de Depósito de Glicogênio Tipo I / Glucose / Hipoglicemia / Lipoproteínas VLDL Tipo de estudo: Etiology_studies Limite: Adult / Aged / Animals / Female / Humans / Male / Middle aged Idioma: En Revista: J Inherit Metab Dis Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Holanda
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Triglicerídeos / Hipertrigliceridemia / Doença de Depósito de Glicogênio Tipo I / Glucose / Hipoglicemia / Lipoproteínas VLDL Tipo de estudo: Etiology_studies Limite: Adult / Aged / Animals / Female / Humans / Male / Middle aged Idioma: En Revista: J Inherit Metab Dis Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Holanda