Gestational high saturated fat diet alters C57BL/6 mouse perinatal skeletal formation

Liang, Chengya; Oest, Megan E.; Jones, Jeryl C.; Prater, M. Renée

doi:10.1002/bdrb.20204

Cited by 44 publications

(34 citation statements)

References 46 publications

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“…Our findings of shortened bone length and matrix maturation in the skeletally immature mice on the HFD are consistent with previous reports that show that bone length and maturation are reduced in the offspring of pregnant mice fed a diet high in fat. (35) In addition, our findings are consistent with recent reports that show small size as well as decreased height in preadolescents and adolescents with hyperlipidemia, (36,37) supporting the need for further investigation into the regulatory mechanism of this phenomenon. Interestingly, changes in serum IGF-1 levels did not correspond with the changes in bone formation.…”

Section: Discussionsupporting

confidence: 92%

Hyperlipidemia induces resistance to PTH bone anabolism in mice via oxidized lipids

Sage

Atti

et al. 2010

Journal of Bone and Mineral Research

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In hyperlipidemia, oxidized lipids accumulate in vascular tissues and trigger atherosclerosis. Such lipids also deposit in bone tissues, where they may promote osteoporosis. We found previously that oxidized lipids attenuate osteogenesis and that parathyroid hormone (PTH) bone anabolism is blunted in hyperlipidemic mice, suggesting that osteoporotic patients with hyperlipidemia may develop resistance to PTH therapy. To determine if oxidized lipids account for this PTH resistance, we blocked lipid oxidation products in hyperlipidemic mice with an ApoA-I mimetic peptide, D-4F, and the bone anabolic response to PTH treatment was assessed. Skeletally immature Ldlr À/À mice were placed on a high-fat diet and treated with D-4F peptide and/or with intermittent PTH(1-34) injections. As expected, D-4F attenuated serum lipid oxidation products and tissue lipid deposition induced by the diet. Importantly, D-4F treatment attenuated the adverse effects of dietary hyperlipidemia on PTH anabolism by restoring micro-computed tomographic parameters of bone quality-cortical mineral content, area, and thickness. D-4F significantly reduced serum markers of bone resorption but not bone formation. PTH and D-4F, together but not separately, also promoted bone anabolism in an alternative model of hyperlipidemia, Apoe À/À mice. In normolipemic mice, D-4F cotreatment did not further enhance the anabolic effects of PTH, indicating that the mechanism is through its effects on lipids. These findings suggest that oxidized lipids mediate hyperlipidemia-induced PTH resistance in bone through modulation of bone resorption. ß

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Section: Discussionsupporting

confidence: 92%

Hyperlipidemia induces resistance to PTH bone anabolism in mice via oxidized lipids

Sage

Atti

et al. 2010

Journal of Bone and Mineral Research

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“…The above-mentioned nutrient imbalances have been associated with compromised prenatal skeletal development, changes in fetal body weight and postnatal growth trajectory and a number of severe pathologies in offspring [31,32]. By contrast, the dose of 5-AZA used in our study induced neither skeletal abnormalities nor fetal or offspring growth retardation.…”

Section: Discussioncontrasting

confidence: 67%

Bone loss in adult offspring induced by low-dose exposure to teratogens

et al. 2011

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Maternal malnutrition during pregnancy was shown by numerous studies to result in the birth of offspring exhibiting altered bone characteristics, which are indicative of bone loss. We hypothesized that not only maternal malnutrition but also some developmental toxicants (teratogens) given at a dose inducing neither structural anomalies nor growth retardation can detrimentally affect skeletal health in adult offspring. To check this hypothesis, pregnant mice were exposed to a single injection of 5-aza-2-deoxycytidine (5-AZA) (a teratogen capable of inducing phocomelia of the hind limbs) at a sub-threshold teratogenic dose. Micro-computed tomography scanning revealed that femora of 5-month-old male offspring exposed in uterus to 5-AZA had trabecular microarchitecture indicative of bone loss. Furthermore, exposure to 5-AZA increased the susceptibility of offspring to postnatal chronic mild stress, which has been shown to induce bone loss in mice. While exploring possible mechanisms underlying this phenomenon, we observed that the expression of some microRNAs, which have been demonstrated as regulators of key osteoblastogenic genes, was altered in hind limb buds of embryos exposed to 5-AZA. Furthermore, the expression of receptor activator of nuclear factor kappa B ligand (RANKL) in femoral stromal/osteoblastic cells of 5-month-old offspring of 5-AZA-treated females was found to be increased. Collectively, this study implies for the first time that single low-dose exposure to a teratogen can induce bone loss in adult offspring, possibly via alteration of embryonic microRNAs and RANKL expression.

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“…Although many studies demonstrate a close relationship between low birth weight and adult-onset diseases (Gale et al, 2001;Gennser et al, 1988;Hales et al, 1991;Ozanne, 2001), birth weight is only a crude summary index of growth, and few studies have been performed that more intricately evaluate parameters of developmental delay as they relate to fetal programming and susceptibility to adult disease (Barker, 1998). Our recent studies evaluated the influence of HFD on fetal skeletal formation in addition to birth weight and length, to more specifically identify relationships between perinatal outcomes and risk of adult-onset bone disease (Liang et al, 2009). The present study supports and extends these prior studies and provides convincing evidence to demonstrate a strong relationship between poor fetal growth and elevated incidence of adult-onset bone disease following poor maternal diet high in saturated fats.…”

Section: Discussionmentioning

confidence: 99%

“…However, few animal studies have been conducted, to date, that mechanistically explain the observations from human populations regarding the contribution of poor prenatal diet such as HFD on future susceptibility to adult-onset osteoporosis. Our initial results revealed fetal skeletal developmental delay following maternal HFD in the mouse model (Liang et al, 2009). In an attempt to understand mechanisms relating fetal environment to the development of chronic adult diseases, the present study is intended to extend the results of our prenatal research of maternal HFD-induced fetal malformation into adulthood.…”

Section: Introductionmentioning

confidence: 93%

Intrauterine exposure to high saturated fat diet elevates risk of adult‐onset chronic diseases in C57BL/6 mice

Liang

Oest

Prater

2009

Birth Defects Research Pt B

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Collectively, these data suggest that offspring of dams who consume a diet rich in saturated fats during pregnancy are at increased risk of adult-onset chronic disease. Additionally, these chronic diseases were determined to be in-part OS-mediated, and preventable by increasing a prenatal dietary antioxidant; this knowledge offers both a putative mechanism of disease pathogenesis and suggests a potential preventive strategy.

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Gestational high saturated fat diet alters C57BL/6 mouse perinatal skeletal formation

Cited by 44 publications

References 46 publications

Hyperlipidemia induces resistance to PTH bone anabolism in mice via oxidized lipids

Hyperlipidemia induces resistance to PTH bone anabolism in mice via oxidized lipids

Bone loss in adult offspring induced by low-dose exposure to teratogens

Intrauterine exposure to high saturated fat diet elevates risk of adult‐onset chronic diseases in C57BL/6 mice

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