title: Genetic Variant in Flavin-Containing Monooxygenase 3 Alters Lipid Metabolism in Laying Hens in a Diet-Specific Manner.
abstract: Genetic variant T329S in flavin-containing monooxygenase 3 (FMO3) impairs trimethylamine (TMA) metabolism in birds. The TMA metabolism that under complex genetic and dietary regulation, closely linked to cardiovascular disease risk. We determined whether the genetic defects in TMA metabolism may change other metabolic traits in birds, determined whether the genetic effects depend on diets, and to identify genes or gene pathways that underlie the metabolic alteration induced by genetic and diet factors. We used hens genotyped asFMO3c.984 A>T as well as those with the homozygous normal genotype. For each genotype, hens were provided with either a corn-soybean meal basal diets (SM), which contains lower levels of TMA precursor, or the basal diets supplemented with 21% of rapeseed meal (RM), which contains higher levels of TMA precursor. An integrative analysis of metabolomic and transcriptomic was used to explore the metabolic patterns ofFMO3genetic variant in hens that were fed the two defined diets. In birds that consumed SM diets, the T329S mutation increased levels of plasma TMA and lipids,FMO3mRNA levels, and the expression of genes involved in long chain polyunsaturated fatty acid biosynthesis. In birds that consumed RM diets, the T329S mutation induced fishy odor syndrome, a repression in LXR pathway and a reciprocal change in lipid metabolism. Variations in TMA and lipid metabolism were linked to the genetic variant inFMO3in a diet-specific manner, which suggest FMO3 functions in TMA metabolism and lipid homeostasis. LXR pathway and polyunsaturated fatty acid metabolism are two possible mechanisms of FMO3 action in response to dietary TMA precursor.
authors.affiliation: Key Laboratory of Feed Biotechnology of Ministry of Agriculture, Feed Research Institute, Chinese Academy of Agricultural Sciences, Beijing 100081, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.affiliation: Key Laboratory of Feed Biotechnology of Ministry of Agriculture, Feed Research Institute, Chinese Academy of Agricultural Sciences, Beijing 100081, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Long
authors.affiliation: Key Laboratory of Feed Biotechnology of Ministry of Agriculture, Feed Research Institute, Chinese Academy of Agricultural Sciences, Beijing 100081, China.
authors.forename: Haijun
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Feed Biotechnology of Ministry of Agriculture, Feed Research Institute, Chinese Academy of Agricultural Sciences, Beijing 100081, China.
authors.forename: Yanan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Feed Biotechnology of Ministry of Agriculture, Feed Research Institute, Chinese Academy of Agricultural Sciences, Beijing 100081, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Wang
authors.affiliation: Key Laboratory of Feed Biotechnology of Ministry of Agriculture, Feed Research Institute, Chinese Academy of Agricultural Sciences, Beijing 100081, China.
authors.forename: Hongyuan
authors.initials: H
authors.lastname: Yue
authors.affiliation: Key Laboratory of Feed Biotechnology of Ministry of Agriculture, Feed Research Institute, Chinese Academy of Agricultural Sciences, Beijing 100081, China.
authors.forename: Xiaocui
authors.initials: X
authors.lastname: Wang
authors.affiliation: Key Laboratory of Feed Biotechnology of Ministry of Agriculture, Feed Research Institute, Chinese Academy of Agricultural Sciences, Beijing 100081, China.
authors.forename: Shugeng
authors.initials: S
authors.lastname: Wu
authors.affiliation: Key Laboratory of Feed Biotechnology of Ministry of Agriculture, Feed Research Institute, Chinese Academy of Agricultural Sciences, Beijing 100081, China.
authors.forename: Guanghai
authors.initials: G
authors.lastname: Qi
mesh_terms: D000821:Animal Feed; D000818:Animals; D029741:Brassica rapa; D002645:Chickens; D004531:Eggs; D005260:Female; D005838:Genotype; D050356:Lipid Metabolism / Q000235:genetics / Q000502:physiology; D008744:Methylamines / Q000378:metabolism; D009154:Mutation; D010105:Oxygenases / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics
chemical_list: D008744:Methylamines; D012333:RNA, Messenger; D010105:Oxygenases; C020066:dimethylaniline monooxygenase (N-oxide forming); C023336:trimethylamine
keywords: dietary TMA precursor; flavin-containing monooxygenase 3; genetic variant; laying hen; lipid metabolism; trimethylamine