Dietary fatty acids regulate hepatic low density lipoprotein (LDL) transport by altering LDL receptor protein and mRNA levels.

Horton, Jay D.; Cuthbert, Jennifer A.; Spady, David K.

doi:10.1172/jci116645

Cited by 94 publications

(59 citation statements)

References 45 publications

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“…Liver LDL-r removes LDL-cholesterol from circulation, thereby maintaining cholesterol homeostasis (12). A high-SFA intake during the postnatal time period has been reported to lower the expression of hepatic LDL-r in several animal models (19,30,31,55) and in human studies (29). The LDL-r mRNA expression was significantly reduced in the female S/S and C/S offspring.…”

Section: Discussionmentioning

confidence: 99%

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Developmental programming of lipid metabolism and aortic vascular function in C57BL/6 mice: a novel study suggesting an involvement of LDL-receptor

Chechi

McGuire²,

Cheema³

2009

American Journal of Physiology-Regulatory, Integrative and Comp

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Chechi K, McGuire JJ, Cheema SK. Developmental programming of lipid metabolism and aortic vascular function in C57BL/6 mice: a novel study suggesting an involvement of LDL-receptor. Am J Physiol Regul Integr Comp Physiol 296: R1029 -R1040, 2009. First published February 4, 2009 doi:10.1152/ajpregu.90932.2008We have previously shown that a maternal high-fat diet, rich in saturated fatty acids (SFA), alters the lipid metabolism of their adult offspring. The present study was designed to investigate 1) whether alterations in hepatic LDL-receptor (LDL-r) expression may serve as a potential mechanism of developmental programming behind the altered lipid metabolism of the offspring, 2) whether altered lipid metabolism leads to aortic vascular dysfunction in the offspring, 3) whether deleterious effects of SFA exposure preweaning are influenced by postweaning diet, and 4) whether gender-specific programming effects are observed. Female C57Bl/6 mice were fed a high-SFA diet or regular chow during gestation and lactation while their pups, both male and female, received either SFA or a chow diet after weaning. Male offspring obtained from mothers fed an SFA diet and those who continued on chow postweaning had higher plasma triglycerides and total cholesterol, whereas female offspring had higher plasma total and LDL cholesterol levels, lower hepatic LDL-r mRNA expression, and reduced aortic contractile responses compared with the offspring that were fed chow throughout the study. A comparison of the postweaning diet revealed significantly lower hepatic LDL-r expression along with significantly higher plasma LDL-cholesterol concentration in the female offspring that were obtained from mothers fed an SFA diet and who continued on an SFA diet postweaning, compared with the female offspring that were obtained from mothers fed an SFA diet but who continued on chow postweaning. In conclusion, we report a novel observation of hepatic LDL-r-mediated programming of altered lipid metabolism, along with aortic vascular dysfunction, in the female offspring of mothers fed a high-SFA diet. Male offspring only exhibited dyslipidemia, suggesting gender-mediated programming. This study further highlighted the role of postweaning diets in overriding the effects of maternal programming. fetal programming; plasma lipids; hepatic LDL-receptor; dietary fats; cardiovascular disease RECENT EVIDENCE BASED ON THE developmental origins of health and disease hypothesis suggests that early nutrition can be critical in determining the cardiovascular health of an individual (43, 44). According to this hypothesis, which was originally known as Barker's hypothesis, an adverse maternal nutrition during gestation can create a stressed environment for the developing fetus. The fetus responds to this nutritional stress by programming its own growth in a way that could increase its risk of developing metabolic disorders in later life (6 -8). Considering that a typical Western diet is rich in dietary fat content (17), especially saturated fatty acids (SFA), s...

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Section: Discussionmentioning

confidence: 99%

“…SFA intake raises plasma LDL levels (54,60) and inhibits the expression of hepatic LDL-receptor (LDL-r) (29,31). Both in vitro and in vivo studies have shown that aortic endothelial function may be abnormal within a few hours of exposure to increased levels of LDL cholesterol (32,40).…”

mentioning

confidence: 99%

Developmental programming of lipid metabolism and aortic vascular function in C57BL/6 mice: a novel study suggesting an involvement of LDL-receptor

Chechi

McGuire²,

Cheema³

2009

American Journal of Physiology-Regulatory, Integrative and Comp

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show abstract

“…Hepatic ACAT activity and cholesteryl ester levels are sensitive to the fatty acid composition of dietary lipid, being higher in animals fed unsaturated fatty acids compared to those fed saturated fatty acids (29,30). We previously showed in the hamster that hepatic LDL receptor …”

Section: Resultsmentioning

confidence: 99%

“…In the hamster, polyunsaturated fatty acids upregulate hepatic LDL receptor expression and lower plasma LDL concentrations when compared to saturated fatty acids (29).…”

Section: Introductionmentioning

confidence: 93%

“…Based on the observation that hepatic ACAT activity is higher in animals fed unsaturated fatty acids than in those fed saturated fatty acids (30), it has been hypothesized that unsaturated fatty acids, by enhancing ACAT activity, may reduce the amount of free cholesterol in a putative regulatory pool that feeds back on LDL receptor expression (27)(28)(29)31,32).…”

Section: Introductionmentioning

confidence: 99%

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Role of Acyl-Coenzyme A:Cholesterol Acyltransferase-1 in the Control of Hepatic VLDL Secretion and LDL Receptor Expression in the Mouse and Hamster

Spady

Willard

Meidell

2000

Journal of Biological Chemistry

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Effects of Essential Fatty Acid Preparation (SR-3) on Brain Lipids, Biochemistry, and Behavioral and Cognitive Functions

Yehuda¹,

Rabinovitz²,

Mostofsky³

1997

Handbook of Essential Fatty Acid Biology

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Dietary fatty acids regulate hepatic low density lipoprotein (LDL) transport by altering LDL receptor protein and mRNA levels.

Cited by 94 publications

References 45 publications

Developmental programming of lipid metabolism and aortic vascular function in C57BL/6 mice: a novel study suggesting an involvement of LDL-receptor

Developmental programming of lipid metabolism and aortic vascular function in C57BL/6 mice: a novel study suggesting an involvement of LDL-receptor

Role of Acyl-Coenzyme A:Cholesterol Acyltransferase-1 in the Control of Hepatic VLDL Secretion and LDL Receptor Expression in the Mouse and Hamster

Effects of Essential Fatty Acid Preparation (SR-3) on Brain Lipids, Biochemistry, and Behavioral and Cognitive Functions

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