3‐HB has been reported to activate its endogenous receptor Gpr109a on cell membranes among various cell signaling functions.[35] Given that 3‐HB was quickly metabolized in vivo and that 3‐HB generated faster outcomes through Gpr109a,[36] it is likely that 3‐HB exerted its protective role in atherosclerosis through activating Gpr109a signaling rather than though other mechanisms requiring chromatin remodeling, especially when Gpr109a is highly expressed in macrophages.[37] 3‐HB effectively reduces IL‐1β (the product of NLRP3 inflammsome activation) secretion (Figure 1). This evidence concerns the gene HCAR2 and atherosclerosis.