The enhancement of fat oxidation during the active phase and suppression of body weight gain in glycerol-3-phosphate dehydrogenase 1 deficient mice

ABSTRACT

We investigated whether the deletion of glycerol-3-phosphate dehydrogenase (GPD) 1 would affect carbohydrate oxidation, fat oxidation, and body weight by using the GPD1 null mice (BALB/cHeA (HeA)). We found that fat oxidation in HeA mice was significantly high during the early active phase than in BALB/cBy (By) mice used as a control under ad libitum conditions. Metabolic tracer experiment revealed that fatty acid oxidation in the skeletal muscle of HeA mice tended to be high. The energy expenditure and fat oxidation in HeA mice under fasting conditions were significantly higher than that in the By mice. Moreover, we monitored body weight gain in HeA mice under ad libitum feeding and found lower body weight gain. These data indicate that GPD1 deficiency induces enhancement of fat oxidation with suppression of weight gain. We propose that GPD1 deletion contributes to the reduction of body weight gain via enhancement of fat oxidation.

GRAPHICAL ABSTRACT

(a) GPD1 deletion lowers cytosolic NAD⁺/NADH ratio and inhibits glycolysis. (b) GPD1 deletion reduces body weight gain due to enhancing energy expenditure and fat oxidation.

KEYWORDS:

• Glycerol-3-phosphate dehydrogenase
• glycerophosphate shuttle
• NAD⁺/NADH ratio
• energy expenditure
• fat oxidation

Acknowledgments

We thank Dr. Nobuko Mori (Osaka Prefecture University, Japan) for the kind gift of the GPD1 null mice (BALB/cHeA mice). Grant-in-Aid for JSPS Research Fellow (KAKENHI, numbers 15J10165) from the Japanese Ministry of Education, Culture, Sports, Science, and Technology (MEXT, Tokyo), the Mishima Kaiun Memorial Foundation (Tokyo, Japan), and a University of Shizuoka Grant for Scientific and Educational Research. We thank the members of the Laboratory of Nutritional Biochemistry (Graduate School of Nutritional and Environmental Sciences, University of Shizuoka) for their technical assistance.

Author contribution

Tomoki Sato and Shinji Miura designed the experiments. Tomoki Sato, Neo Sayama and Mizuki Inoue performed mouse experiment. Tomoki Sato, Akihito Morita and Shinji Miura interpreted the results and analyzed the data. Tomoki Sato and Shinji Miura prepared figures and wrote the manuscript. All authors reviewed the results and approved the final version of the manuscript.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was supported by [Japan Society for the Promotion of Science] under Grant [KAKENHI, numbers 15J10165]; [Mishima Kaiun Memorial Foundation] under Grant [None]; [University of Shizuoka Grant for Scientific and Educational Research] under Grant [None].