Mice with severe mitochondrial disease have largely normal response to fasting

What is it about?

We subjected mice to a short fast (withdrawal of food for a certain period of time), which in healthy mice and humans switches the energy metabolism from burning glucose to fat. This as accompanied by other typical changes such as decrease in blood glucose and increase in blood ketones and free fatty acids. We knew beforehand that Bcs1l mutant mice, which mimic human CIII deficiency very well, quickly lose all white fat after weaning (3 weeks of age), and they accumulate fat in the liver in a way that is typical of fasting. Subjecting the mice to fasting allowed us to test if this is a normal lipolytic response to energy deficiency. Quite surprisingly, the sick mice responded to a short fast almost identically to wild-type littermates. The only parameters where they differed were lower ketones and glycerol in the plasma of mutant mice. A likely explanations for these interesting differences is that both glycerol (resulting from degradation of triglycerides) and ketone bodies were quickly taken up into tissues and used for energy.

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Why is it important?

This is one of the very few - if not the only - study of basic lipid mobilization and plasma lipid profiles in a mouse model of mitochondrial disease. It gives important insight about the regulation of nutrient metabolism in mitochondrial disease.