Effects of long-chain, saturated fatty acids on membrane microviscosity and adrenocorticotropin responsiveness of human adrenocortical cells in vitro.
Open accessAbstract
Adrenoleukodystrophy (ALD) and adrenomyeloneuropathy are inherited disorders in which long-chain, saturated fatty acids (LCFA) accumulate in various tissues. A mechanism by which LCFA cause the endocrine and neurological dysfunction characteristic of these diseases is proposed based on in vitro response of human adrenocortical cells to ACTH in the presence of various fatty acids. Human adrenocortical cells cultured in the presence of 5 microM hexacosanoic (C26:0) or lignoceric (C24:0) acids showed decreased basal and ACTH-stimulated cortisol release compared with cells cultured without exogenous fatty acids or in the presence of linoleic acid (C18:2). Measurement of fluorescence polarization demonstrates a significant increase in the membrane microviscosity of cells cultured in the presence of LCFA. It is hypothesized that cells exposed to LCFA have increased membrane microviscosity with a consequent decrease in their ability to respond to ACTH. This decrease in trophic support may contribute to the adrenal insufficiency and atrophy in patients with ALD.
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Adrenal cell function is disrupted by altered microviscosity of the cell membrane when exposed to C26:0, leading to impaired response to ACTH stimulation.
“Furthermore, function of adrenal cells has been witnessed to be disrupted by altered microviscosity of the cell-membrane when exposed to C26:0, leading to an impaired response to adrenocorticotropin (ACTH) stimulation (20).”
From X-linked adrenoleukodystrophy and primary adrenal insufficiency (2023) · cites this paper as [20]
The Discussion reports that human adrenocortical cells incubated with long-chain fatty acids had increased membrane microviscosity and an impaired response to ACTH; the reported experiments include hexacosanoic acid (C26:0). It proposes, rather than establishes, that the microviscosity change causes the impaired response. The supplied Discussion passages do not specify a page. (LLM, conf=0.86)
Experimental — accuracy not yet measuredElevated levels of VLCFA have been shown to be detrimental to adrenocortical cells in culture and to model membranes.
“although elevated levels of VLCFA have been shown to be detrimental to adrenocortical cells in culture (34,42) and to model membranes (43).”
From Functional overlap between ABCD1 (ALD) and ABCD2 (ALDR) transporters: a therapeutic target for X-adrenoleukodystrophy (2004) · cites this paper as [42]
The membrane of adrenal cells is disrupted by altered microviscosity when exposed to C26:0, which supposedly leads to impaired response to adrenocorticotropic hormone.
“The membrane of adrenal cells is disrupted by altered microviscosity when exposed to C26:0, which supposedly leads to impaired response to adrenocorticotropic hormone (ACTH) [425].”
From Revisiting the Pathogenesis of X-Linked Adrenoleukodystrophy (2025) · cites this paper as [425]
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Cites
Fluidity parameters of lipid regions determined by fluorescence polarization
Shinitzky, M., & Barenholz, Y. (1978) · Biochimica et Biophysica Acta (BBA) - Reviews on Biomembranes · doi:10.1016/0304-4157(78)90010-2 · Cited by 1,882 · see citing works
Microviscosity parameters and protein mobility in biological membranes
Shinitzky, M., & Inbar, M. (1976) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/0005-2736(76)90183-8 · Cited by 676 · see citing works
Lentz, B. R., Barenholz, Y., & Thompson, T. E. (1976) · Biochemistry · doi:10.1021/bi00665a030 · Cited by 491 · see citing works
Qualitative alteration in substrate specificity of mitochondrial monoamine oxidase in brain
Moskvitina, T. A., Kamyshanskaya, N. S., Kaverina, L. P., & Gorkin, V. Z. (1976) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1976.tb04462.x · Cited by 440 · see citing works
Physical Principles and Techniques of Protein Chemistry
(1969) · Elsevier eBooks · doi:10.1016/b978-0-12-440101-3.50001-1 · Cited by 261 · see citing works
Adrenoleukodystrophy: Survey of 303 cases: Biochemistry, diagnosis, and therapy
Moser, H. W., Moser, A. E., Singh, I., & OʼNeill, P. (1984) · Annals of Neurology · doi:10.1002/ana.410160603 · Cited by 259 · see citing works
Singh, I., Moser, A. E., Moser, H. W., & Kishimoto, Y. (1984) · Pediatric Research · doi:10.1203/00006450-198403000-00016 · Cited by 234 · see citing works
Griffin, J. W., Goren, E. N., Schaumburg, H. H., Engel, W. K., & LORIAUX, L. D. (1977) · Neurology · doi:10.1212/wnl.27.12.1107 · Cited by 229 · see citing works
Kelley, R. I., Datta, N. S., Dobyns, W. B., Hajra, A. K., Moser, A. B., Noetzel, M. J., Zackai, E. H., Moser, H. W., Opitz, J. M., & Reynolds, J. F. (1986) · American Journal of Medical Genetics · doi:10.1002/ajmg.1320230404 · Cited by 219 · see citing works
Orly, J., & Schramm, M. (1975) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.72.9.3433 · Cited by 186 · see citing works
Rizzo, W. B., Watkins, P. A., Phillips, M. W., Cranin, D., Campbell, B. D., & Avigan, J. (1986) · Neurology · doi:10.1212/wnl.36.3.357 · Cited by 153 · see citing works
Peroxisomal Defects in Neonatal-Onset and X-Linked Adrenoleukodystrophies
Goldfischer, S. L., Collins, J. C., Rapin, I., Coltoff-Schiller, B., Chang, C., Nigro, M. A., Black, V. H., Javitt, N. B., Moser, H. W., & Lazarow, P. B. (1985) · Science · doi:10.1126/science.3964959 · Cited by 151 · see citing works
Moser, A. B., Borel, J. S., Odone, A., Naidu, S., Cornblath, D., Sanders, D. B., & Moser, H. W. (1987) · Annals of Neurology · doi:10.1002/ana.410210305 · Cited by 130 · see citing works
Adrenoleukodystrophy: Dietary oleic acid lowers hexacosanoate levels
Rizzo, W. B., Phillips, M. W., Dammann, A. L., Leshner, R. T., Jennings, S. S., Avigan, J., & Proud, V. K. (1987) · Annals of Neurology · doi:10.1002/ana.410210304 · Cited by 97 · see citing works
Knazek, R. A., Rizzo, W. B., Schulman, J. D., & Dave, J. R. (1983) · Journal of Clinical Investigation · doi:10.1172/jci110963 · Cited by 94 · see citing works
Self-citationMenkes (1977) · doi:10.1212/wnl.27.10.928 · Cited by 78 · see citing works
Brown, F. R., Duyn, M. A. V., Moser, A. B., Schulman, J. D., Rizzo, W. B., Snyder, R. D., Murphy, J. V., Kamoshita, S., Migeon, C. J., & Moser, H. W. (1982) · PubMed · Cited by 56 · see citing works
Duyn, M. A. V., Moser, A. E., Brown, F. R., Sacktor, N., Liu, A., & Moser, H. W. (1984) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/40.2.277 · Cited by 53 · see citing works
The relation between lipid mobility and the specific hormone binding of thyroid membranes
Bashford, C. L., Harrison, S. J., Radda, G. K., et al. (1975) · Biochemical Journal · doi:10.1042/bj1460473 · Cited by 47 · see citing works
Abnormalities in Cultured Muscle and Peripheral Nerve of a Patient with Adrenomyeloneuropathy
Askanas, V., McLaughlin, J., Engel, W. K., & Adornato, B. T. (1979) · New England Journal of Medicine · doi:10.1056/nejm197909133011105 · Cited by 45 · see citing works
Dave, J. R., Knazek, R. A., & Liu, S. C. (1981) · Biochemical and Biophysical Research Communications · doi:10.1016/0006-291x(81)90510-6 · Cited by 37 · see citing works
Self-citationDietary Essential Fatty Acids Are Required for Maintenance and Induction of Prolactin Receptors
Knazek, R. A., & Liu, S. (1979) · Experimental Biology and Medicine · doi:10.3181/00379727-162-40679 · Cited by 36 · see citing works
Self-citationProstaglandin I2 modifies both prolactin binding capacity and fluidity of mouse liver membranes.
Dave, J. R., & Knazek, R. A. (1980) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.77.11.6597 · Cited by 36 · see citing works
Self-citationKnazek, R. A., Liu, S. C., Dave, J. R., et al. (1981) · Prostaglandins and Medicine · doi:10.1016/0161-4630(81)90072-0 · Cited by 31 · see citing works
Self-citationDave, J. R., & Witorsch, R. J. (1984) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/0005-2736(84)90149-4 · Cited by 23 · see citing works
Danforth, D. R., Wells, M. A., & Stouffer, R. L. (1985) · Endocrinology · doi:10.1210/endo-117-2-755 · Cited by 11 · see citing works
ACTH RECEPTOR DEFECT IN ADRENOLEUKODYSTROPHY (ALD)
Meyer, W. J., Smith, E. H., Richards, G. E., et al. (1987) · Pediatric Research · doi:10.1203/00006450-198704010-00502 · Cited by 7 · see citing works
Effects of dietary essential fatty acids on murine mammary gland development.
Knazek, R. A., & Liu, S. C. (1981) · PubMed · Cited by 6 · see citing works
Self-citation
Flagged first, then by citations
Research works printed but not linked: 1
- Knazek, R. A., S. C. Liu, L. M. St. Amand, J. R. Dave, and R. J. Christy. 1981. Cholesterol accentuates the effect of unsaturated fatty acid deficiency on mammary gland development. Proc. Am. Assoc. Cancer Res. 22:28. (Abstr.)
Cited by
Sorted by citations
Borkman, M., Storlien, L. H., Pan, D. A., Jenkins, A. B., Chisholm, D. J., & Campbell, L. V. (1993) · New England Journal of Medicine · doi:10.1056/nejm199301283280404 · Cited by 835 · see citing works
Aubourg, P., Blanche, S., Jambaqué, I., Rocchiccioli, F., Kalifa, G., Naud-Saudreau, C., Rolland, M.-O., Debré, M., Chaussain, J.-L., Griscelli, C., et al. (1990) · New England Journal of Medicine · doi:10.1056/nejm199006283222607 · Cited by 366 · see citing works
X-linked adrenoleukodystrophy: Clinical, metabolic, genetic and pathophysiological aspects
Kemp, S., Berger, J., & Aubourg, P. (2012) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2012.03.012 · Cited by 283 · see citing works
Adrenoleukodystrophy—Neuroendocrine pathogenesis and redefinition of natural history
Kemp, S., Huffnagel, I. C., Linthorst, G. E., Wanders, R. J., & Engelen, M. (2016) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2016.90 · Cited by 275 · see citing works
Pujol, A. (2002) · Human Molecular Genetics · doi:10.1093/hmg/11.5.499 · Cited by 214 · see citing works
Early oxidative damage underlying neurodegeneration in X-adrenoleukodystrophy
Fourcade, S., Lopez-Erauskin, J., Galino, J., Duval, C., Naudi, A., Jove, M., Kemp, S., Villarroya, F., Ferrer, I., Pamplona, R., et al. (2008) · Human Molecular Genetics · doi:10.1093/hmg/ddn085 · Cited by 214 · see citing works
Peroxisomal Disorders: Genotype, Phenotype, Major Neuropathologic Lesions, and Pathogenesis
Powers, J. M., & Moser, H. W. (1998) · Brain Pathology · doi:10.1111/j.1750-3639.1998.tb00139.x · Cited by 208 · see citing works
Pujol, A., Ferrer, I., Camps, C., Metzger, E., Hindelang, C., Callizot, N., Ruiz, M., Pàmpols, T., Giròs, M., & Mandel, J. L. (2004) · Human Molecular Genetics · doi:10.1093/hmg/ddh323 · Cited by 201 · see citing works
Adrenomyeloneuropathy: A Neuropathologic Review Featuring Its Noninflammatory Myelopathy
Powers, J. M., DeCiero, D. P., Ito, M., Moser, A. B., & Moser, H. W. (2000) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/59.2.89 · Cited by 204 · see citing works
Ho, J. K., Moser, H., Kishimoto, Y., & Hamilton, J. A. (1995) · Journal of Clinical Investigation · doi:10.1172/jci118182 · Cited by 199 · see citing works
Very long chain fatty acids in higher animals: a review
Poulos, A. (1995) · Lipids · doi:10.1007/bf02537036 · Cited by 192 · see citing works
X-Linked Adrenoleukodystrophy: Pathogenesis and Treatment
Engelen, M., Kemp, S., & Poll-The, B.-T. (2014) · Current Neurology and Neuroscience Reports · doi:10.1007/s11910-014-0486-0 · Cited by 187 · see citing works
The role of ELOVL1 in very long-chain fatty acid homeostasis and X-linked adrenoleukodystrophy
Ofman, R., Dijkstra, I. M. E., van Roermund, C. W. T., Burger, N., Turkenburg, M., van Cruchten, A., van Engen, C. E., Wanders, R. J. A., & Kemp, S. (2010) · EMBO Molecular Medicine · doi:10.1002/emmm.201000061 · Cited by 170 · see citing works
Biochemical aspects of X-linked adrenoleukodystrophy
Kemp, S., & Wanders, R. (2010) · Brain Pathology · doi:10.1111/j.1750-3639.2010.00391.x · Cited by 116 · see citing works
Fatty Acids - Induced Lipotoxicity and Inflammation
Savary, S., Trompier, D., Andreoletti, P., Le Borgne, F., Demarquoy, J., & Lizard, G. (2012) · Current Drug Metabolism · doi:10.2174/138920012803762729 · Cited by 111 · see citing works
Asheuer, M., Bieche, I., Laurendeau, I., Moser, A., Hainque, B., Vidaud, M., & Aubourg, P. (2005) · Human Molecular Genetics · doi:10.1093/hmg/ddi140 · Cited by 86 · see citing works
Nerve conduction studies in adrenomyeloneuropathy
Chaudhry, V, Moser, H. W., & Cornblath, D. R. (1996) · Journal of Neurology, Neurosurgery & Psychiatry · doi:10.1136/jnnp.61.2.181 · Cited by 73 · see citing works
Fourcade, S., López-Erauskin, J., Ruiz, M., Ferrer, I., & Pujol, A. (2014) · Biochimie · doi:10.1016/j.biochi.2013.09.012 · Cited by 55 · see citing works
Microglial dysfunction as a key pathological change in adrenomyeloneuropathy
Gong, Y., Sasidharan, N., Laheji, F., Frosch, M., Musolino, P., Tanzi, R., Kim, D. Y., Biffi, A., El Khoury, J., & Eichler, F. (2017) · Annals of Neurology · doi:10.1002/ana.25085 · Cited by 54 · see citing works
X-linked adrenoleukodystrophy and primary adrenal insufficiency
Cappa, M., Todisco, T., & Bizzarri, C. (2023) · Frontiers in Endocrinology · doi:10.3389/fendo.2023.1309053 · Cited by 28 · see citing works
Pillai, B. K., Jasuja, R., Simard, J. R., & Hamilton, J. A. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.043737 · Cited by 27 · see citing works
Revisiting the Pathogenesis of X-Linked Adrenoleukodystrophy
Bougnères, P., & Le Stunff, C. (2025) · Genes · doi:10.3390/genes16050590 · Cited by 11 · see citing works
- Authors
- Whitcomb, R. W., Linehan, W. M., & Knazek, R. A.
- Affiliations
- National Institutes of Health (US)
- ORCID
- Linehan, W M
- Venue
- Journal of Clinical Investigation
- Published
- 1988-01-01
- Volume
- 81
- Issue
- 1
- Pages
- 185-188
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC442491
- OpenAlex
- W2012361337
- Cited by
- 168
- References
- 28
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 5 · 2023: 5 · 2022: 3 · 2021: 4 · 2020: 8 · 2019: 3 · 2018: 3 · 2017: 5 · 2016: 10 · 2015: 4 · 2014: 6 · 2013: 5 · 2012: 7
- FWCI
- 3.11
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Lipid Membrane Structure and Behavior
- Keywords
- long-chain saturated fatty acids, adrenoleukodystrophy, adrenomyeloneuropathy, membrane microviscosity, adrenocortical cells, ACTH response, cortisol secretion, hexacosanoic acid, lignoceric acid, linoleic acid, adrenal insufficiency, fatty acid accumulation
- MeSH terms
- Adrenal Cortex, Adrenocorticotropic Hormone, Cell Membrane Permeability, Fatty Acids, Humans, Hydrocortisone, Linolenic Acids, Viscosity, alpha-Linolenic Acid
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