Protein‐enriched extracts from housefly (Musca domestica) maggots alleviates atherosclerosis in apolipoprotein E‐deficient mice by promoting bile acid production and consequent cholesterol consumption

Currently, atherosclerosis control is important to prevent future heart attacks or strokes. Protein‐enriched extract (PE) from housefly maggots (Musca domestica) can inhibit the development of atherosclerosis partially through its antioxidant effects. Whether PE exerts other anti‐atherosclerosis functions remains unclear. Here, PE was found to simultaneously promote cholesterol metabolism effects in apolipoprotein E knockout (ApoE−/−) mice. Bile acid synthesis plays a key role in regulating cholesterol homeostasis in atherosclerosis. Whether PE alleviates atherosclerosis by promoting bile acid production and consequent cholesterol consumption was further explored. First, 8‐week‐old male ApoE−/− mice were recruited and fed on a cholesterol‐enriched diet. After 8 weeks, these mice were divided into three groups and received gavage administration of PE, simvastatin, and saline for another 8 weeks. Atherosclerosis severity was then assessed. Real‐time quantitative polymerase chain reaction and western blot were employed to determine the expression of hepatic ATP‐binding cassette transporter A1 (ABCA1), liver X receptor α (LXRα), and peroxisome proliferator‐activated receptor‐γ (PPAR‐γ). Serum levels of high‐density lipoprotein‐cholesterol (HDL), low‐density lipoprotein‐cholesterol (LDL), and total cholesterol (TC) were determined by enzyme‐linked immunoassay. Results revealed that PE reversed the formation of atherosclerotic lesion; increased the expression of PPAR‐γ, LXRα, and ABCA1; increased the amount of bile flow and total bile acid; reduced the serum level of LDL and TC; and increased the level of HDL. In conclusion, enhancement on bile acid production and consequent cholesterol consumption may partially contribute to the anti‐atherosclerotic effects of PE. The reversal of PPARγ‐LXRα‐ABCA1 signaling pathway may be involved in this process. Highlights 1. Protein extract (PE) from housefly maggots could increase the bile metabolism of the ApoE−/− mice. 2. PE modulates bile metabolism through the PPARγ‐LXRα‐ABCA1 signaling pathway 3. The antiatherosclerosis mechanism of PE might be systematic and thus has a good prospect of clinical transformation. Protein‐enriched extracts from housefly (Musca domestica) maggots can promote the reverse cholesterol transport in APOE−/− mice via PPARγ‐LXRα‐ABCA1 signaling pathway to increase high‐density lipoprotein (HDL) generation in blood and to effectively increase bile flow and total bile acid. This effect ultimately re