title: Calcium supplementation increases circulating cholesterol by reducing its catabolism via GPER and TRPC1-dependent pathway in estrogen deficient women.
abstract: BACKGROUND
  Limited studies have addressed the effects of calcium supplementation (CaS) on serum total cholesterol (TC) in postmenopausal women and the results are inconclusive. Moreover, the potential mechanisms through which CaS regulates cholesterol metabolism in the absence of estrogen are still sealed for the limitation of human being study.
  
  
  METHODS
  Cross-sectional survey, animal and in vitro experiments were conducted to investigate the effect of CaS on endogenous cholesterol metabolism in estrogen deficiency and identify its potential mechanisms. Ovariectomized rats were used to mimic estrogen deficiency. In vitro, HepG2 cell line was exposed to estradiol and/or calcium treatment.
  
  
  RESULTS
  We demonstrated that CaS significantly increased serum TC and the risk of hypercholesterolemia and myocardial infarction in postmenopausal women. Increased serum TC in estrogen deficiency was caused mainly by decreased cholesterol catabolism rather than increased synthesis. This was mediated by reduced 7α-hydroxylase resulting from increased liver intracellular Ca(2+) concentrations, reduced intracellular basal cAMP and subsequent up-regulation of SREBP-1c and SHP expression. Estrogen had a protective role in preventing CaS-induced TC increase by activating the G-protein coupled estrogen receptor, which mediated the estrogen effect through the transient receptor potential canonical 1 cation channel.
  
  
  CONCLUSIONS
  CaS increases endogenous serum TC via decreasing hepatic cholesterol catabolism in estrogen deficiency. G-protein coupled estrogen receptor is shown to be a key target in mediating CaS-induced TC increase. CaS should be monitored for the prevention of serum TC increase during menopause.
authors.affiliation: Department of Nutrition and Food Hygiene, Public Health College, Harbin Medical University, Harbin, China.
authors.forename: Songtao
authors.initials: S
authors.lastname: Li
authors.forename: Ying
authors.initials: Y
authors.lastname: Li
authors.forename: Hua
authors.initials: H
authors.lastname: Ning
authors.forename: Lixin
authors.initials: L
authors.lastname: Na
authors.forename: Yucun
authors.initials: Y
authors.lastname: Niu
authors.forename: Maoqing
authors.initials: M
authors.lastname: Wang
authors.forename: Rennan
authors.initials: R
authors.lastname: Feng
authors.forename: Liyan
authors.initials: L
authors.lastname: Liu
authors.forename: Fuchuan
authors.initials: F
authors.lastname: Guo
authors.forename: Shaoying
authors.initials: S
authors.lastname: Hou
authors.forename: Xia
authors.initials: X
authors.lastname: Chu
authors.forename: Yemei
authors.initials: Y
authors.lastname: Wang
authors.forename: Yunbo
authors.initials: Y
authors.lastname: Zhang
authors.forename: Huaqi
authors.initials: H
authors.lastname: Zhang
authors.forename: Lina
authors.initials: L
authors.lastname: Huang
authors.forename: Mingxin
authors.initials: M
authors.lastname: Bi
authors.forename: Yifan
authors.initials: Y
authors.lastname: Huang
authors.forename: Liuyi
authors.initials: L
authors.lastname: Hao
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhao
authors.forename: Cheng
authors.initials: C
authors.lastname: Wang
authors.forename: Yanwen
authors.initials: Y
authors.lastname: Wang
authors.forename: Yonghan
authors.initials: Y
authors.lastname: He
authors.forename: Changhao
authors.initials: C
authors.lastname: Sun
mesh_terms: D000818:Animals; D002118:Calcium / Q000008:administration & dosage*; D002784:Cholesterol / Q000097:blood* / Q000378:metabolism; D003430:Cross-Sectional Studies; D019587:Dietary Supplements; D004967:Estrogens / Q000172:deficiency*; D005260:Female; D051381:Rats; D017208:Rats, Wistar; D043562:Receptors, G-Protein-Coupled / Q000502:physiology*; D050052:TRPC Cation Channels / Q000502:physiology*
chemical_list: D004967:Estrogens; C520305:Gper1 protein, rat; D043562:Receptors, G-Protein-Coupled; D050052:TRPC Cation Channels; C096351:transient receptor potential cation channel, subfamily C, member 1; D002784:Cholesterol; D002118:Calcium
keywords: Calcium supplementation; Cholesterol; Estrogen; G-Protein coupled estrogen receptor