A. Sato, H. Nemoto, A. Yabuki, G. Sato, Y. Ogawa and M. Ohira (2025). The role of ketone bodies in oxidized LDL-induced cell proliferation and lipid accumulation of macrophages. International journal of experimental pathology, 106(4), e70002. https://doi.org/10.1111/iep.70002

PubMed 40448300

[Abstract]
Ketone bodies (KBs), which include β-hydroxybutyric acid (β-HB) and acetoacetic acid (AcAc), play critical roles in organismal energy homeostasis; however, their effects on atherosclerosis remain unknown. In this study, we investigated the role of β-HB and AcAc on proliferation and lipid accumulation in macrophages by the uptake of oxidized LDL (Ox-LDL), causing the formation of atherosclerotic plaques, using mouse macrophage J774A.1 cells. Both β-HB and AcAc reduced cell proliferation, and AcAc increased lipid accumulation in Ox-LDL-treated J774A.1 cells. Western blotting showed that Ox-LDL decreased the protein expression of two KB-specific receptors, GPR41 and GPR43, both of which are known as potent modulators of inflammation, but had negligible effects on that of the β-HB-specific GPR109A in the cells. These results suggest that Ox-LDL may induce inflammatory responses by decreasing the protein expression of GPR41 and GPR43 in macrophages, and that AcAc, but not β-HB, may exacerbate Ox-LDL-caused atherosclerosis.