Age- and sex-related differences in extra-hepatic low-density lipoprotein receptor
Abstract
To determine whether differences in LDLr behavior in extra‐hepatic tissues and whether extra‐hepatic receptors could differentially contribute to cholesterol homeostasis under physiological conditions, we evaluated the presence and regulation of LDLr from both a gender and an aging perspective. We used the brain cortex, the gastrocnemius, and the heart ventricle of 3‐ and 12‐month‐old male and female rats. We observed a protein decrease of total LDLr in 12‐month‐old female rat brains that was completely restored by 17‐β estradiol treatment. In the gastrocnemius, LDLr accumulates in the skeletal muscle in both male and female aged rats as a precursor probably due to a glycosylation impairment. In the heart, no modifications were observed in either older rats or rats of a specific gender. These data highlight a tissue‐specific dysregulation of LDLr that is age‐ and gender‐dependent. J. Cell. Physiol. 226: 2610–2616, 2011. © 2010 Wiley‐Liss, Inc.
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Our research group demonstrated that cholesterol biosynthesis and uptake are differently modulated in different brain regions of adult male rats, with HMGCR activity very low in the brain stem and high in hippocampus, brain cortex and cerebellum.
“In particular, our research group demonstrated that cholesterol biosynthesis and uptake are differently modulated in different brain regions of adult male rats. The HMGCR activity is very low in the brain stem, and high in hippocampus, brain cortex and cerebellum.”
From Loss of Mevalonate/Cholesterol Homeostasis in the Brain: A Focus on Autism Spectrum Disorder and Rett Syndrome (2019) · cites this paper as [23]
These changes suggest that low intracellular cholesterol content, as a consequence of HMGCR activity suppression in RTT fibroblasts, induces the classic feedback mechanism with activation of SREBP2 and the increase of its transcriptional targets such as LDLR and HMGCR.
“These changes suggest that low intracellular cholesterol content, as a consequence of HMGCR activity suppression in RTT fibroblasts, induces the classic feedback mechanism with activation of SREBP2 and the increase of its transcriptional targets such as LDLR (LDL receptor) and HMGCR [23,55,103,104,105,106,107].”
From Loss of Mevalonate/Cholesterol Homeostasis in the Brain: A Focus on Autism Spectrum Disorder and Rett Syndrome (2019) · cites this paper as [23]
Cites
Gender differences in the incidence of AD and vascular dementia: The EURODEM Studies
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Lipoprotein receptors in the liver. Control signals for plasma cholesterol traffic.
Brown, M. S., & Goldstein, J. L. (1983) · Journal of Clinical Investigation · doi:10.1172/jci111044 · Cited by 545 · see citing works
Cholesterol: From Feeding to Gene Regulation
Martini, C., & Pallottini, V. (2007) · Genes & Nutrition · doi:10.1007/s12263-007-0049-y · Cited by 53 · see citing works
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Can Cholesterol Metabolism Modulation Affect Brain Function and Behavior?
Cartocci, V., Servadio, M., Trezza, V., & Pallottini, V. (2017) · Journal of Cellular Physiology · doi:10.1002/jcp.25488 · Cited by 77 · see citing works
Self-citationSegatto, M., Tonini, C., Pfrieger, F. W., Trezza, V., & Pallottini, V. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20133317 · Cited by 51 · see citing works
“These regional differences depend on sex- and age-specific metabolic regulation [22,23].”
BackgroundSelf-citationSegatto, M., Manduca, A., Lecis, C., Rosso, P., Jozwiak, A., Swiezewska, E., Moreno, S., Trezza, V., & Pallottini, V. (2014) · Neuropsychopharmacology · doi:10.1038/npp.2013.284 · Cited by 51 · see citing works
Self-citationTrapani, L. (2013) · World Journal of Hepatology · doi:10.4254/wjh.v5.i12.676 · Cited by 14 · see citing works
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- Authors
- Segatto, M., Trapani, L., Marino, M., & Pallottini, V.
- Affiliations
- Roma Tre University (IT)
- Corresponding author
- Pallottini, Valentina
- Venue
- Journal of Cellular Physiology
- Publisher
- Wiley
- Published
- 2011-07-22
- Volume
- 226
- Issue
- 10
- Pages
- 2610-2616
- ISSN
- 0021-9541 (ISSN-L)
- 1097-4652
- OpenAlex
- W2071682678
- Cited by
- 37
- References
- 3
- Citations by year
- 2025: 2 · 2024: 1 · 2023: 2 · 2021: 3 · 2020: 5 · 2019: 3 · 2018: 3 · 2017: 2 · 2016: 2 · 2015: 1 · 2014: 4 · 2013: 5 · 2012: 3
- FWCI
- 3.04
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Cellular Physiology (publishedVersion)
- PubMed (publishedVersion)
- Archivio Istituzionale della Ricerca - Università degli Studi del Molise (submittedVersion)
- IRIS Research product catalog (Sapienza University of Rome) (submittedVersion)
- Iris (Roma Tre University) (submittedVersion)
- Topics
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
- Keywords
- LDL receptor, aging, sex differences, cholesterol homeostasis, estradiol, cerebral cortex, skeletal muscle, cardiac ventricle, receptor glycosylation
- MeSH terms
- Age Factors, Animals, Cerebral Cortex, Female, Liver, Male, Myocardium, Organ Specificity, Receptors, LDL, Sex Characteristics, Rats, Wistar, Muscle, Skeletal, Rats
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