Impaired amino acid metabolism contributes to fasting-induced hypoglycemia in fatty acid oxidation defects

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Impaired amino acid metabolism contributes to fasting-induced hypoglycemia in fatty acid oxidation defects. / Houten, Sander M.; Herrema, Hilde ; te Brinke, Heleen et al.

In: Human molecular genetics, Vol. 22, No. 25, 2013, p. 5249-5261.

Research output: Contribution to journal › Article › Academic › peer-review

BibTeX

@article{537cdae7db124b6fb7e52c4536239eb8,

title = "Impaired amino acid metabolism contributes to fasting-induced hypoglycemia in fatty acid oxidation defects",

abstract = "The importance of mitochondrial fatty acid β-oxidation (FAO) as a glucose-sparing process is illustrated by patients with inherited defects in FAO, who may present with life-threatening fasting-induced hypoketotic hypoglycemia. It is unknown why peripheral glucose demand outpaces hepatic gluconeogenesis in these patients. In this study, we have systematically addressed the fasting response in long-chain acyl-CoA dehydrogenase-deficient (LCAD KO) mice. We demonstrate that the fasting-induced hypoglycemia in LCAD KO mice was initiated by an increased glucose requirement in peripheral tissues, leading to rapid hepatic glycogen depletion. Gluconeogenesis did not compensate for the increased glucose demand, which was not due to insufficient hepatic glucogenic capacity but rather caused by a shortage in the supply of glucogenic precursors. This shortage in supply was explained by a suppressed glucose-alanine cycle, decreased branched-chain amino acid metabolism and ultimately impaired protein mobilization. We conclude that during fasting, FAO not only serves to spare glucose but is also indispensable for amino acid metabolism, which is essential for the maintenance of adequate glucose production",

author = "Houten, {Sander M.} and Hilde Herrema and {te Brinke}, Heleen and Simone Denis and Ruiter, {Jos P. N.} and {van Dijk}, {Theo H.} and Argmann, {Carmen A.} and Roelof Ottenhoff and Michael M{\"u}ller and Groen, {Albert K.} and Folkert Kuipers and Dirk-Jan Reijngoud and Wanders, {Ronald J. A.}",

year = "2013",

doi = "10.1093/hmg/ddt382",

language = "English",

volume = "22",

pages = "5249--5261",

journal = "Human molecular genetics",

issn = "0964-6906",

publisher = "Oxford University Press",

number = "25",

}

RIS

TY - JOUR

T1 - Impaired amino acid metabolism contributes to fasting-induced hypoglycemia in fatty acid oxidation defects

AU - Houten, Sander M.

AU - Herrema, Hilde

AU - te Brinke, Heleen

AU - Denis, Simone

AU - Ruiter, Jos P. N.

AU - van Dijk, Theo H.

AU - Argmann, Carmen A.

AU - Ottenhoff, Roelof

AU - Müller, Michael

AU - Groen, Albert K.

AU - Kuipers, Folkert

AU - Reijngoud, Dirk-Jan

AU - Wanders, Ronald J. A.

PY - 2013

Y1 - 2013

N2 - The importance of mitochondrial fatty acid β-oxidation (FAO) as a glucose-sparing process is illustrated by patients with inherited defects in FAO, who may present with life-threatening fasting-induced hypoketotic hypoglycemia. It is unknown why peripheral glucose demand outpaces hepatic gluconeogenesis in these patients. In this study, we have systematically addressed the fasting response in long-chain acyl-CoA dehydrogenase-deficient (LCAD KO) mice. We demonstrate that the fasting-induced hypoglycemia in LCAD KO mice was initiated by an increased glucose requirement in peripheral tissues, leading to rapid hepatic glycogen depletion. Gluconeogenesis did not compensate for the increased glucose demand, which was not due to insufficient hepatic glucogenic capacity but rather caused by a shortage in the supply of glucogenic precursors. This shortage in supply was explained by a suppressed glucose-alanine cycle, decreased branched-chain amino acid metabolism and ultimately impaired protein mobilization. We conclude that during fasting, FAO not only serves to spare glucose but is also indispensable for amino acid metabolism, which is essential for the maintenance of adequate glucose production

AB - The importance of mitochondrial fatty acid β-oxidation (FAO) as a glucose-sparing process is illustrated by patients with inherited defects in FAO, who may present with life-threatening fasting-induced hypoketotic hypoglycemia. It is unknown why peripheral glucose demand outpaces hepatic gluconeogenesis in these patients. In this study, we have systematically addressed the fasting response in long-chain acyl-CoA dehydrogenase-deficient (LCAD KO) mice. We demonstrate that the fasting-induced hypoglycemia in LCAD KO mice was initiated by an increased glucose requirement in peripheral tissues, leading to rapid hepatic glycogen depletion. Gluconeogenesis did not compensate for the increased glucose demand, which was not due to insufficient hepatic glucogenic capacity but rather caused by a shortage in the supply of glucogenic precursors. This shortage in supply was explained by a suppressed glucose-alanine cycle, decreased branched-chain amino acid metabolism and ultimately impaired protein mobilization. We conclude that during fasting, FAO not only serves to spare glucose but is also indispensable for amino acid metabolism, which is essential for the maintenance of adequate glucose production

U2 - 10.1093/hmg/ddt382

DO - 10.1093/hmg/ddt382

M3 - Article

C2 - 23933733

VL - 22

SP - 5249

EP - 5261

JO - Human molecular genetics

JF - Human molecular genetics

SN - 0964-6906

IS - 25

ER -

ID: 2243407

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