Fasting reveals largely intact systemic lipid mobilization mechanisms in respiratory chain complex III deficient mice

Publication date: Available online 29 October 2019Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Nikica Tomašić, Heike Kotarsky, Rejane de Oliveira Figueiredo, Eva Hansson, Matthias Mörgelin, Ivan Tomašić, Jukka Kallijärvi, Eskil Elmér, Matti Jauhiainen, Erik A. Eklund, Vineta FellmanAbstractMice homozygous for the human GRACILE syndrome mutation (Bcs1lc.A232G) display decreased respiratory chain complex III activity, liver dysfunction, hypoglycemia, rapid loss of white adipose tissue and early death. To assess the underlying mechanism of the lipodystrophy in homozygous mice (Bcs1lp.S78G), these and wild-type control mice were subjected to a short 4-hour fast. The homozygotes had low baseline blood glucose values, but a similar decrease in response to fasting as in wild-type mice, resulting in hypoglycemia in the majority. Despite the already depleted glycogen and increased triacylglycerol content in the mutant livers, the mice responded to fasting by further depletion and increase, respectively. Increased plasma free fatty acids (FAs) upon fasting suggested normal capacity for mobilization of lipids from white adipose tissue into circulation. Strikingly, however, serum glycerol concentration was not increased concomitantly with free FAs, suggesting its rapid uptake into the liver and utilization for fuel or gluconeogenesis in the mutants. The mutant hepatocyte mitochondria were capable of responding to fasting by appropriate morphol...

Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - October 29, 2019 Category: Molecular Biology Source Type: research