Differential effects of polyunsaturated fatty acids on sterol synthesis rates in adult and fetal tissues of the hamster: consequence of altered sterol balance

Schmid, Kara; Woollett, Laura A.

doi:10.1152/ajpgi.00226.2003

Cited by 11 publications

(11 citation statements)

References 58 publications

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“…While HMGR can be ubiquinated in the presence of sterol [41], it is further ubiquinated in the presence of both sterol plus geranylgeraniol, implying involvement of a geranylgeranylated protein [57], or plus lanosterol [58]. These more recent data support the observations that maximal suppression of sterol synthesis rates occurs only in the presence of cholesterol plus a mevalonate-derived product [18,59], which may be absent in a tissue in a negative sterol balance and/or proliferating rapidly as during development [49]. Additionally, a lack of HMGR degradation in the fetal tissues could be due to the fact that HMGR degradation is accelerated by binding to Insig-1 [41].…”

Section: Hmgr Degradationsupporting

confidence: 78%

“…Also, Insig-1 is stabilized when sterols are present [22,23]. If there is no abundance of sterols due to their requirement for membrane formation during rapid growth, Insig-1 may be ubiquintated and degraded rapidly during the fetal period as seen by low protein levels [48], supporting our hypothesis that the fetus is in a negative sterol balance [49]. Regardless, other factors besides the ratio of SCAP to Insig-1 must be involved in responsiveness of sterol synthesis rates to exogenous sterol since a correlation did not exist between the ratio of mRNA of these two proteins and the degree of suppressed synthesis rates in the fetal liver, placenta, and yolk sac.…”

Section: Constitutive Processing Of Srebp-2mentioning

confidence: 75%

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Inability to fully suppress sterol synthesis rates with exogenous sterol in embryonic and extraembyronic fetal tissues

Yao

Jenkins

Horn

et al. 2007

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

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SUMMARYThe requirement for cholesterol is greater in developing tissues (fetus, placenta, and yolk sac) as compared to adult tissues. Here, we compared cholesterol-induced suppression of sterol synthesis rates in the adult liver to the fetal liver, fetal body, placenta, and yolk sac of the Golden Syrian hamster. Sterol synthesis rates were suppressed maximally in non-pregnant adult livers when cholesterol concentrations were increased. In contrast, sterol synthesis rates were suppressed only marginally in fetal livers, fetal bodies, placentas, and yolk sacs when cholesterol concentrations were increased. To begin to elucidate the mechanism responsible for the blunted response of sterol synthesis rates in fetal tissues to exogenous cholesterol, the ratio of sterol regulatory element-binding protein (SREBP) cleavage-activating protein (SCAP) to Insig-1 was measured in these same tissues since the ratio of SCAP to the Insigs can impact SREBP processing. The fetal tissues had anywhere from a 2-to 6-fold greater ratio of SCAP to Insig-1 than did the adult liver, suggesting constitutive processing of the SREBPs. As expected, the level of mature, nuclear SREBP-2 was not different in the fetal tissues with different levels of cholesterol whereas it was different in adult livers. These findings indicate that the suppression of sterol synthesis to exogenous sterol is blunted in developing tissues and the lack of response appears to be mediated at least partly through relative levels of Insigs and SCAP.

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Section: Hmgr Degradationsupporting

confidence: 78%

Section: Constitutive Processing Of Srebp-2mentioning

confidence: 75%

Inability to fully suppress sterol synthesis rates with exogenous sterol in embryonic and extraembyronic fetal tissues

Yao

Jenkins

Horn

et al. 2007

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

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“…Because of their high proliferation and membrane formation rates, embryonic and fetal cells have elevated cholesterol requirements. Interestingly, these cells do not suppress cholesterol synthesis in response to rises in ER sterol concentration (Schmid & Woollett, ; Yao et al ., ), possibly as an adaptation to secure sufficient cholesterol supply. Mechanistically, this lack of feedback regulation seems to result from SREBP constitutive processing and activation, as a consequence of higher SCAP/INSIG ratios in the ER membrane (Yao et al ., ).…”

Section: Cholesterol Physiological Regulation and Pathological Implicmentioning

confidence: 97%

Retracted: Advances in the physiological and pathological implications of cholesterol

et al. 2013

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Cholesterol has evolved to fulfill sophisticated biophysical, cell signalling, and endocrine functions in animal systems. At the cellular level, cholesterol is found in membranes where it increases both bilayer stiffness and impermeability to water and ions. Furthermore, cholesterol is integrated into specialized lipid-protein membrane microdomains with critical topographical and signalling functions. At the organismal level, cholesterol is the precursor of all steroid hormones, including gluco- and mineralo-corticoids, sex hormones, and vitamin D, which regulate carbohydrate, sodium, reproductive, and bone homeostasis, respectively. This sterol is also the immediate precursor of bile acids, which are important for intestinal absorption of dietary lipids as well as energy homeostasis and glucose regulation. Complex mechanisms maintain cholesterol within physiological ranges and the dysregulation of these mechanisms results in embryonic or adult diseases, caused by either excessive or reduced tissue cholesterol levels. The causative role of cholesterol in these conditions has been demonstrated by genetic and pharmacological manipulations in animal models of human disease that are discussed herein. Importantly, the understanding of basic aspects of cholesterol biology has led to the development of high-impact pharmaceutical therapies during the past century. The continuing effort to offer successful treatments for prevalent cholesterol-related diseases, such as atherosclerosis and neurodegenerative disorders, warrants further interdisciplinary research in the coming decades.

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“…In adults, LXR is affected by unsaturated fatty acids (17). It is not unusual for the fetus to respond differently to exogenous factors compared with adults, however, since fetal sterol synthesis does not change in response to exogenous cholesterol and polyunsaturated fatty acids as do adults (61,81). Likewise, the lack of effect on fetal HNF-4␣ might not be unexpected, since the previously reported increase in this signaling factor occurred in fetal livers of monkeys fed diets with higher levels of saturated fat and cholesterol compared with our mice, which were fed more unsaturated fat and no cholesterol (45).…”

Section: Discussionmentioning

confidence: 99%

Dietary fat impacts fetal growth and metabolism: uptake of chylomicron remnant core lipids by the placenta

Rebholz

Burke

Yang

et al. 2011

American Journal of Physiology-Endocrinology and Metabolism

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The fetus requires significant energy for growth and development. Although glucose is a major source of energy for the fetus, other maternal nutrients also appear to promote growth. Thus, the goal of these studies was to determine whether triglyceride-rich remnants are taken up by the placenta and whether maternal dietary lipids, independently of adiposity, can impact fetal growth. To accomplish our first goal, chylomicron particles were duallly labeled with cholesteryl ester and triglycerides. The placenta took up remnant particles/core lipids at rates greater than adipose tissue and skeletal muscle but less than the liver. Although the placenta expresses apoE receptors, uptake of chylomicron remnants and/or core lipids can occur independently of apoE. To determine the impact of dietary lipid on fetal growth, independent of maternal adiposity, females were fed high-fat diets (HFD) for 1 mo; there was no change in adiposity or leptin levels prior to or during pregnancy of dams fed HFD. Fetal masses were greater in dams fed HFD, and mRNA levels of proteins involved in fatty acid oxidation (CPT I, PPARα), but not glucose oxidation (pyruvate kinase) or other regulatory processes (HNF-4α, LXR), were increased with maternal dietary fat. There was also no change in mRNA levels of proteins involved in placental glucose and fatty acid transport, and GLUT1 protein levels in microvillous membranes were similar in placentas of dams fed either diet. Thus, the ability of the placenta to take up chylomicron remnant core lipids likely contributes to accelerated fetal growth in females fed high fat diets.

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Differential effects of polyunsaturated fatty acids on sterol synthesis rates in adult and fetal tissues of the hamster: consequence of altered sterol balance

Cited by 11 publications

References 58 publications

Inability to fully suppress sterol synthesis rates with exogenous sterol in embryonic and extraembyronic fetal tissues

Inability to fully suppress sterol synthesis rates with exogenous sterol in embryonic and extraembyronic fetal tissues

Retracted: Advances in the physiological and pathological implications of cholesterol

Dietary fat impacts fetal growth and metabolism: uptake of chylomicron remnant core lipids by the placenta

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