Fatty acid oxidation alleviates the energy deficiency caused by the loss of MPC1 in MPC1 mice.

Pyruvate is a central substrate in energy metabolism, paramount to carbohydrate, fat, and amino acid catabolic and anabolic pathways. Mitochondrial pyruvate carrier 1(MPC1) is one important component of the complex that facilitates mitochondrial pyruvate import. Complete MPC1 deficiency is a serious concern, and has been shown to result in embryonic lethality in mice. The study outlined in this paper generated one mouse line with the MPC1 protein part deficiency by using the CRISPR/Cas9 system. Clinical observations, body weight and organ/tissue weight, gas exchange, cold-stimulation, blood parameters, as well as histopathology analysis were analyzed to evaluate potential physiological abnormalities caused by MPC1 deficiency. Results indicate that MPC1 mice experienced a change in important clinical criteria such as low body weight, decreased movement, and low body shell temperature, few adipose accumulate. The mice show significant difference in some blood parameters including apo-B100, apo-A1, HDL, glucagon, insulin. However these changes alleviated while being fed with the HFD, which provided metabolites to sustain the TCA cycle and body development. The MPC1 mice may employ fatty acid oxidation to meet their bioenergetic demands. This study suggests that inhibition of MPC1 activity can boost fatty acid oxidation to provide sufficient energy to the body. This work promotes further studies regarding the interplay between carbohydrate and fat metabolism.