T329S Mutation in the FMO3 Gene Alleviates Lipid Metabolic Diseases in Chickens in the Late Laying Period

Abstract

The T329S mutation in flavin-containing monooxygenase 3 (FMO3) impairs the trimethylamine (TMA) metabolism in laying hens. The TMA metabolic pathway is closely linked to lipid metabolic diseases, such as atherosclerosis and fatty liver disease. We aimed to evaluate the effects of the T329S mutation in FMO3 on lipid metabolism in chickens during the late laying period. We selected 18 FMO3 genotyped individuals (consisting of six AA, six AT, and six TT hens) with similar body weight and production performance. The lipid metabolism and deposition characteristics of the laying hens with different genotypes were compared. The T329S mutation moderated the serum-lipid parameters in TT hens compared to those in AA and AT hens from 49 to 62 weeks. Furthermore, it reduced the serum trimethylamine N-oxide concentrations and increased the serum total bile acid (p < 0.05) and related lipid transporter levels in TT hens. Moreover, it significantly (p < 0.01) decreased atherosclerotic lesions and hepatic steatosis in TT hens compared to those in the AA and AT hens. Our findings may help improve the health status in laying hens during the late laying period.

Associations of the T329S Polymorphism in Flavin-Containing Monooxygenase 3 With Atherosclerosis and Fatty Liver Syndrome in 90-Week-Old Hens

“…Accordingly, the decreased trends of TC and LDL-C levels of TT hens explained the decrease in AS lesions. However, the observed trend of plasma VLDL levels of TT hens is inconsistent with that of our previous study, which showed that TT hens have higher VLDL levels at 62 weeks ( 19 ). This might be related to hepatic TG secretion because VLDL is the major transport vehicle for TG from the liver to extrahepatic tissues, or it might be attributable to the dynamic change of VLDL subclasses in layers during the normal aging process ( 25 , 41 ).…”

“…During the present study, our results showed that the T329S mutation in FMO3 decreased the AL and AAL in TT hens compared to those in AA and AT hens at 90 weeks. This result is consistent with our previous observations, which showed that T329S reduced AS lesions in a strain of chickens laying brown eggs at 62 weeks ( 19 ). This result can be attributed to T329S diminishing the activity of the TMAO-generating enzyme FMO3 and therefore decreased the plasma circulating TMAO concentrations in TT hens.…”

“…These results implied that the T329S mutation could alter cholesterol and lipid metabolism of laying hens. The decreasing trends of plasma TC and LDL-C levels of TT hens are consistent with our previous findings, which showed that T329S moderated the serum lipid parameters of TT hens compared to those of AA and AT hens from 49 to 62 weeks ( 19 ). It is known that higher plasma TC and LDL-C levels could increase the risk of AS; however, modulating these cholesterol levels can reduce the incidence of diseases in older laying hens ( 32 , 40 ).…”

“…TMAO has been shown to suppress reverse cholesterol transport and affect lipid absorption and cholesterol homeostasis by inhibiting bile acid synthesis, and to subsequently induce cholesterol accumulation in macrophages, finally resulting in the development of AS ( 7 – 9 , 37 ). In contrast, a decrease in the plasma TMAO concentration associated with an increase in the bile acid pool has been suggested as a possible mechanism of the T329S mutation involved in the reduction of AS lesions in chickens ( 19 ). Therefore, these results confirmed that the spontaneous mutation in FMO3 could alleviate AS lesions in layers.…”

“…Subsequently, Guo ( 17 ) confirmed this claim by showing FMO3 enzyme activity in TT hens (T329S homozygous mutants) was significantly lower than those of AA (wild-type) and AT (heterozygous mutants) hens. Because the regulation of cholesterol disposal in poultry is highly similar to that in mammals, laying hens could be used as an animal model to further explore the relationship between FMO3 and AS ( 18 , 19 ). Additionally, it is generally accepted that AS, fatty liver syndrome (FLS), and adiposity are closely linked in animals, including layers ( 20 – 22 ).…”