Caffeine-induced fetal rat over-exposure to maternal glucocorticoid and histone methylation of liver IGF-1 might cause skeletal growth retardation

Tan, Yang; Liu, Jin; Deng, Yu; Cao, Hong; Xu, Dan; Cu, Fenglong; Lei, You-ying; Magdalou, Jacques; Wu, Min; Chen, Liaobin; Wang, Hui

doi:10.1016/j.toxlet.2012.09.007

Cited by 100 publications

(99 citation statements)

References 55 publications

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“…Increased promoter methylation in the F1 IUGR rat liver dampens IGF-1 expression in what is also thought to be an additional epigenetically mediated adaptive mechanism (33). It is well established that the IGF-1 gene sequence has variable epigenetic regulation, and accompanying transcriptional changes have been shown repeatedly and by multiple investigators (33,35,39,54). Despite this, the mechanisms for multigenerational inheritance observed here are thus far unclear.…”

Section: Discussionmentioning

confidence: 82%

Essential nutrient supplementation prevents heritable metabolic disease in multigenerational intrauterine growth‐restricted rats

et al. 2014

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Intrauterine growth restriction (IUGR) confers heritable alterations in DNA methylation, rendering risk of adult metabolic syndrome (MetS). Because CpG methylation is coupled to intake of essential nutrients along the one-carbon pathway, we reasoned that essential nutrient supplementation (ENS) may abrogate IUGRconferred multigenerational MetS. Pregnant SpragueDawley rats underwent bilateral uterine artery ligation causing IUGR in F1. Among the F2 generation, IUGR lineage rats were underweight at birth (6.7 vs. 8.0 g, P < 0.0001) and obese by adulthood (p160: 613 vs. 510 g; P < 0.0001). Dual energy X-ray absorptiometry studies revealed increased central fat mass (D+40 g), accompanied by dyslipidemic (>30% elevated, P < 0.05) serum triglycerides (139 mg/dl), very-LDLs (27.8 mg/dl), and fatty acids (632 mM). Hyperglycemic-euglycemic clamp studies and glucose tolerance testing revealed insulin resistance. Conversely, IUGR lineage ENS-fed rats did not manifest MetS, with significantly lower body weight (p160: 410 g), >5-fold less central fat mass, normal hepatic glucose efflux, and >70% reduced circulating triglycerides and veryLDLs compared with IUGR control-fed F2 offspring (P < 0.01). Moreover, increased methylation of the IGF-1 P2 transcriptional start site among IUGR lineage F2 offspring was reversed in ENS (P < 0.04). This is an initial demonstration that supplementation along the one-carbon pathway abrogates adult morbidity and associated epigenomic modifications of IGF-1 in a rodent model of multigenerational MetS.-Goodspeed, D., Seferovic, M. D., Holland, W., Mcknight, R. A., Summers, S. A., Branch, D. W., Lane, R. H., Aagaard, K. M. Essential nutrient supplementation prevents heritable metabolic disease in multigenerational intrauterine growth-restricted rats. FASEB J. 29, 807-819 (2015). www.fasebj.org

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Section: Discussionmentioning

confidence: 82%

Essential nutrient supplementation prevents heritable metabolic disease in multigenerational intrauterine growth‐restricted rats

et al. 2014

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“…11 The choice of dose levels was based on literature data coupled with preliminary dose-response studies to avoid sublethal effects at the top dose level. 8,9 The median lethal dose of caffeine administered orally to rats is known to be 192 mg/kg. 12 The highest dose (120 mg/kg) was chosen in this study based on the study, which showed no renal toxicity and demonstrated inhibition of long bone growth in prepubertal rats.…”

Section: Animalsmentioning

confidence: 99%

“…Caffeine adversely affects endochondral ossification during the course of fetal skeletal growth, and maternal exposure to caffeine causes delayed and abnormal fetal skeletal development. [7][8][9] Although caffeine's detrimental effects on endochondral ossification during the prenatal period have been widely demonstrated, data on its effects on longitudinal bone growth during the pubertal growth spurt are particularly sparse. To the best of our knowledge, there are no interventional studies dedicated to assessing the effects of different doses and exposure durations of caffeine on skeletal development during puberty.…”

Section: Introductionmentioning

confidence: 99%

Peripubertal Caffeine Exposure Impairs Longitudinal Bone Growth in Immature Male Rats in a Dose- and Time-Dependent Manner

Choi

Kim

et al. 2016

Journal of Medicinal Food

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This study investigated the dose- and time-dependent effects of caffeine consumption throughout puberty in peripubertal rats. A total of 85 male SD rats were randomly divided into four groups: control and caffeine-fed groups with 20, 60, or 120 mg/kg/day through oral gavage for 10, 20, 30, or 40 days. Caffeine decreased body weight gain and food consumption in a dose- and time-dependent manner, accompanied by a reduction in muscle and body fat. In addition, it caused a shortening and lightening of leg bones and spinal column. The total height of the growth plate decreased sharply at 40 days in the controls, but not in the caffeine-fed groups, and the height of hypertrophic zone in the caffeine-fed groups was lower than in the control. Caffeine increased the height of the secondary spongiosa, whereas parameters related to bone formation, such as bone area ratio, thickness and number of trabeculae, and bone perimeter, were significantly reduced. Furthermore, serum levels of IGF-1, estradiol, and testosterone were also reduced by the dose of caffeine exposure. Our results demonstrate that caffeine consumption can dose- and time-dependently inhibit longitudinal bone growth in immature male rats, possibly by blocking the physiologic changes in body composition and hormones relevant to bone growth.

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“…Fetal blood samples were collected, and the serum were separated to measure CORT concentrations following the protocol of the ELISA kit (Shen et al, 2014). Fetal femora were immediately harvested for length measurement and histological analyses, including histochemical staining, immunohistochemical assays and genes expression analysis (Tan et al, 2012).…”

Section: / 31mentioning

confidence: 99%

Suppressed osteoclast differentiation at the chondro-osseous junction mediates endochondral ossification retardation in long bones of Wistar fetal rats with prenatal ethanol exposure

Pan

Zhang

Shangguan

et al. 2016

Toxicology and Applied Pharmacology

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Caffeine-induced fetal rat over-exposure to maternal glucocorticoid and histone methylation of liver IGF-1 might cause skeletal growth retardation

Cited by 100 publications

References 55 publications

Essential nutrient supplementation prevents heritable metabolic disease in multigenerational intrauterine growth‐restricted rats

Essential nutrient supplementation prevents heritable metabolic disease in multigenerational intrauterine growth‐restricted rats

Peripubertal Caffeine Exposure Impairs Longitudinal Bone Growth in Immature Male Rats in a Dose- and Time-Dependent Manner

Suppressed osteoclast differentiation at the chondro-osseous junction mediates endochondral ossification retardation in long bones of Wistar fetal rats with prenatal ethanol exposure

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