Adenylate kinase 5 deficiency impairs epididymal white adipose tissue homeostasis and decreases fat mass.

Abstract

Importance: The brain and adipose tissue interact metabolically, and if there is a problem with the energy metabolism of the brain, it cannot maintain the energy balance with the adipose tissue. Therefore, when adenylate kinase 5 (AK5), which regulates energy metabolism in the brain, is knocked out, problems with lipid metabolism may occur.

Objective: We aimed to elucidate the metabolic function and phenotype of AK5, a gene with an unknown function in metabolism.

Methods: We generated AK5 knockout (KO) mice and administered high-fat and fasting diets to the mice to confirm their physiological phenotype and metabolic differences.

Results: In the high-fat diet (HFD) test, no differences in body weight, epididymal white adipose tissue (eWAT), or fat mass of AK5 KO mice were observed. In indirect calorimetry, the respiratory exchange ratio and activity counts increased in normal chow diet mice, but there was no difference between the HFD groups. At the mRNA level, there were no significant differences in the expression of lipid metabolism markers between wild-type and AK5 KO mice. Still, the glucose signal of adipocytes increased in AK5 KO mice. In the fasting test, the eWAT of AK5 KO mice was significantly reduced, as was the expression of lipid metabolism and inflammation-related immune markers. Thus, the apoptosis of adipocytes increased, and an imbalance in energy metabolism occurred.

Conclusions and relevance: When AK5 KO mice are energy deficient, it becomes difficult to use eWAT for energy storage, imbalance occurs, and apoptosis of adipocytes in eWAT increases.