title: Prenatal caffeine ingestion induces transgenerational neuroendocrine metabolic programming alteration in second generation rats.
abstract: Our previous studies have demonstrated that prenatal caffeine ingestion induces an increased susceptibility to metabolic syndrome with alterations of glucose and lipid metabolic phenotypes in adult first generation (F1) of intrauterine growth retardation (IUGR) rats, and the underlying mechanism is originated from a hypothalamic-pituitary-adrenal (HPA) axis-associated neuroendocrine metabolic programming alteration in utero. This study aims to investigate the transgenerational effects of this programming alteration in adult second generation (F2). Pregnant Wistar rats were administered with caffeine (120mg/kg·d) from gestational day 11 until delivery. Four groups in F2 were set according to the cross-mating between control and caffeine-induced IUGR rats. F2 were subjected to a fortnight ice water swimming stimulus on postnatal month 4, and blood samples were collected before and after stress. Results showed that the majority of the activities of HPA axis and phenotypes of glucose and lipid metabolism were altered in F2. Particularly, comparing with the control group, caffeine groups had an enhanced corticosterone levels after chronic stress. Compared with before stress, the serum glucose levels were increased in some groups whereas the triglyceride levels were decreased. Furthermore, total cholesterol gain rates were enhanced but the high-density lipoprotein-cholesterol gain rates were decreased in most caffeine groups after stress. These transgenerational effects were characterized partially with gender and parental differences. Taken together, these results indicate that the reproductive and developmental toxicities and the neuroendocrine metabolic programming mechanism by prenatal caffeine ingestion have transgenerational effects in rats, which may help to explain the susceptibility to metabolic syndrome and associated diseases in F2.
authors: Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071, China; Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071, China.
authors: Hanwen
authors: H
authors: Luo
authors: Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071, China.
authors: Zixin
authors: Z
authors: Deng
authors: Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071, China.
authors: Lian
authors: L
authors: Liu
authors: Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071, China.
authors: Lang
authors: L
authors: Shen
authors: Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071, China.
authors: Hao
authors: H
authors: Kou
authors: Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071, China.
authors: Zheng
authors: Z
authors: He
authors: Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071, China; Research Center of Food and Drug Evaluation, Wuhan University, Wuhan 430071, China.
authors: Jie
authors: J
authors: Ping
authors: Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071, China; Research Center of Food and Drug Evaluation, Wuhan University, Wuhan 430071, China.
authors: Dan
authors: D
authors: Xu
authors: Department of Epidemiology & Health Statistics, Public Health School of Wuhan University, Wuhan 430071, China.
authors: Lu
authors: L
authors: Ma
authors: Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071, China. Electronic address: lbchen@whu.edu.cn.
authors: Liaobin
authors: L
authors: Chen
authors: Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071, China; Research Center of Food and Drug Evaluation, Wuhan University, Wuhan 430071, China. Electronic address: wanghui19@whu.edu.cn.
authors: Hui
authors: H
authors: Wang
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D002110:Caffeine / Q000008:administration & dosage / Q000009:adverse effects*; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D003345:Corticosterone / Q000097:blood; D004305:Dose-Response Relationship, Drug; D005260:Female; D005317:Fetal Growth Retardation / Q000473:pathology; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000503:physiopathology*; D050356:Lipid Metabolism / Q000187:drug effects; D008297:Male; D009490:Neurosecretory Systems / Q000187:drug effects* / Q000378:metabolism; D010913:Pituitary-Adrenal System / Q000187:drug effects / Q000503:physiopathology*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000503:physiopathology*; D051381:Rats; D017208:Rats, Wistar; D012098:Reproduction / Q000187:drug effects; D013312:Stress, Physiological / Q000187:drug effects; D014280:Triglycerides / Q000097:blood
chemical_list: D001786:Blood Glucose; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D014280:Triglycerides; D002110:Caffeine; D003345:Corticosterone
keywords: 11β-HSD2; 11β-hydroxysteroid dehydrogenase 2; ACTH; CORT; Caffeine; Chronic stimulation; F1; F2; GC; GD; GR; Glucose and lipid metabolism; HDL-C; HPA; Hypothalamus–pituitary–adrenal axis; IUGR; Intrauterine growth retardation; LDL-C; MR; MS; PM; PW; TCH; TG; Transgenerational inheritance; adrenocorticotropin-releasing hormone; corticosterone; first generation; gestational day; glucocorticoid; glucocorticoid receptor; high-density lipoprotein-cholesterol; hypothalamic–pituitary–adrenal; intrauterine growth retardation; low-density lipoprotein-cholesterol; metabolic syndrome; mineralocorticoid receptor; postnatal month; postnatal week; second generation; total cholesterol; triglyceride