title: Lipidomic profiling reveals significant alterations in lipid biochemistry in hypothyroid rat cerebellum and the therapeutic effects of Sini decoction.
abstract: Hypothyroidism is known to be closely associated with lipid metabolism. Although our previous serum and urine metabonomics studies have provided some clues about the molecular mechanism of hypothyroidism at the metabolic level, the precise mechanism underlying the pathogenesis of hypothyroidism remains elusive, especially from the aspect of lipid metabolism. In the present study, we applied an ultra high performance liquid chromatography/time-of-flight mass spectrometry (UHPLC/TOF-MS)-based lipidomics method to analyze the global lipid profiles of hypothyroidism in rat cerebellum. Using unsupervised analysis and multivariate statistical analysis, we separated the Sham and hypothyroid groups clearly and screened out 23 potential lipid biomarkers related to hypothyroidism that were primarily involved in sphingolipid metabolism, glycerophospholipid metabolism and β-oxidation of fatty acid. Subsequently, we conducted computational analysis to build and simulate the lipid network of hypothyroidism, knowing that it would be useful to elucidate the pathological mechanism of hypothyroidism. Based on the selected 23 lipid biomarkers, we systematically evaluated the therapeutic effects of Sini decoction (SND) and the positive drug T4. The results showed that both SND and T4 can to some extent convert the pathological status of hypothyroidism through different pathways. Overall, this investigation illustrates that lipidomic profiling approach is powerful in giving a complementary view to the pathophysiology of hypothyroidism and offers a valuable tool for systematic study of the therapeutic effects of SND on hypothyroidism at lipid level.
authors.affiliation: School of Pharmacy, Second Military Medical University, Shanghai 200433, China.
authors.forename: Si
authors.initials: S
authors.lastname: Wu
authors.affiliation: School of Pharmacy, Second Military Medical University, Shanghai 200433, China.
authors.forename: Si
authors.initials: S
authors.lastname: Chen
authors.affiliation: School of Pharmacy, Second Military Medical University, Shanghai 200433, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Dong
authors.affiliation: School of Pharmacy, Second Military Medical University, Shanghai 200433, China; School of Pharmacy, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Guangguo
authors.initials: G
authors.lastname: Tan
authors.affiliation: School of Pharmacy, Second Military Medical University, Shanghai 200433, China.
authors.forename: Wuhong
authors.initials: W
authors.lastname: Li
authors.affiliation: School of Pharmacy, Second Military Medical University, Shanghai 200433, China.
authors.forename: Ziyang
authors.initials: Z
authors.lastname: Lou
authors.affiliation: School of Pharmacy, Second Military Medical University, Shanghai 200433, China. Electronic address: zzyzyfzhu@163.com.
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Zhu
authors.affiliation: School of Pharmacy, Second Military Medical University, Shanghai 200433, China. Electronic address: yfchai@smmu.edu.cn.
authors.forename: Yifeng
authors.initials: Y
authors.lastname: Chai
mesh_terms: D000818:Animals; D002531:Cerebellum / Q000378:metabolism*; D004365:Drugs, Chinese Herbal / Q000494:pharmacology / Q000627:therapeutic use*; D007037:Hypothyroidism / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism*; D050356:Lipid Metabolism; D008297:Male; D055432:Metabolomics; D017208:Rats, Wistar; D013972:Thyrotropin / Q000097:blood; D013974:Thyroxine / Q000097:blood; D014284:Triiodothyronine / Q000097:blood
chemical_list: D004365:Drugs, Chinese Herbal; C478756:sini tang; D014284:Triiodothyronine; D013972:Thyrotropin; D013974:Thyroxine
keywords: Cerebellum; Hypothyroidism; Lipidomic profiling; Sini decoction; Traditional Chinese medicine; Ultra high performance liquid chromatography–mass spectrometry