The role of ketone bodies in oxidized LDL‐induced cell proliferation and lipid accumulation of macrophages

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.