Sphingolipids and Cholesterol

Li, Zhiqiang

doi:10.1007/978-981-19-0394-6_1

Cited by 15 publications

(5 citation statements)

References 165 publications

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Section: Discussionmentioning

confidence: 99%

“…Excess lipids can increase AD pathology through multiple mechanisms. Lipid rafts of sphingomyelin and cholesterol in neuronal membranes facilitate Aβ splicing (Beel et al, 2010; Jiang & Li, 2022; Lee et al, 2021; Reitz et al, 2004), whereas dispersing these lipid rafts promotes alternative splicing into a harmless peptide (Grimm et al, 2008; Marenchino et al, 2008; Runz et al, 2002). Increasing brain cholesterol by preventing efflux to the bloodstream is sufficient to produce soluble Aβ and memory deficits in WT mice (Djelti et al, 2015), and our AD rats on either diet showed decreased expression of cytochrome P450 family 46 subfamily A member 1 ( Cyp46a1 ), the rate‐limiting enzyme for brain cholesterol efflux, and increased expression of Stard4 , which allows lipids to freely cross the outer mitochondrial membrane (Miller & Bose, 2011).…”

Section: Discussionmentioning

confidence: 99%

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Obesity during preclinical Alzheimer's disease development exacerbates brain metabolic decline

Anderson

Sharma

Kelberman

et al. 2023

Journal of Neurochemistry

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Alzheimer's disease (AD) is the most common form of dementia. Obesity in middle age increases AD risk and severity, which is alarming given that obesity prevalence peaks at middle age and obesity rates are accelerating worldwide. Midlife, but not late‐life obesity increases AD risk, suggesting that this interaction is specific to preclinical AD. AD pathology begins in middle age, with accumulation of amyloid beta (Aβ), hyperphosphorylated tau, metabolic decline, and neuroinflammation occurring decades before cognitive symptoms appear. We used a transcriptomic discovery approach in young adult (6.5 months old) male and female TgF344‐AD rats that overexpress mutant human amyloid precursor protein and presenilin‐1 and wild‐type (WT) controls to determine whether inducing obesity with a high‐fat/high‐sugar “Western” diet during preclinical AD increases brain metabolic dysfunction in dorsal hippocampus (dHC), a brain region vulnerable to the effects of obesity and early AD. Analyses of dHC gene expression data showed dysregulated mitochondrial and neurotransmission pathways, and up‐regulated genes involved in cholesterol synthesis. Western diet amplified the number of genes that were different between AD and WT rats and added pathways involved in noradrenergic signaling, dysregulated inhibition of cholesterol synthesis, and decreased intracellular lipid transporters. Importantly, the Western diet impaired dHC‐dependent spatial working memory in AD but not WT rats, confirming that the dietary intervention accelerated cognitive decline. To examine later consequences of early transcriptional dysregulation, we measured dHC monoamine levels in older (13 months old) AD and WT rats of both sexes after long‐term chow or Western diet consumption. Norepinephrine (NE) abundance was significantly decreased in AD rats, NE turnover was increased, and the Western diet attenuated the AD‐induced increases in turnover. Collectively, these findings indicate obesity during prodromal AD impairs memory, potentiates AD‐induced metabolic decline likely leading to an overproduction of cholesterol, and interferes with compensatory increases in NE transmission.image

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Obesity during preclinical Alzheimer's disease development exacerbates brain metabolic decline

Anderson

Sharma

Kelberman

et al. 2023

Journal of Neurochemistry

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“…The digestion and utilization of dietary sphingolipids starts in the jejunum section of the small intestine. The typical plasma membrane of mammalian cells contains about 20% cholesterol, 15–20% sphingomyelin, and 5% glycolipids of the total lipids, whereas the small intestinal brush border contains about 10% cholesterol, 5% sphingomyelin and over 30% glycolipids of the total lipids ( 7 , 94 ). Bouhours and Guignard detected 750 nmol of sphingomyelin, 160 nmol of free ceramide, and 390 nmol of glucosylceramide from 1 mL of isolated rat intestinal epithelial cells ( 95 ).…”

Section: Absorption and Utilization Of Dietary Sphingomyelinmentioning

confidence: 99%

The nutritional functions of dietary sphingomyelin and its applications in food

Yang

Chen

2022

Front. Nutr.

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Sphingolipids are common structural components of cell membranes and are crucial for cell functions in physiological and pathophysiological conditions. Sphingomyelin and its metabolites, such as sphingoid bases, ceramide, ceramide-1-phosphate, and sphingosine-1-phosphate, play signaling roles in the regulation of human health. The diverse structures of sphingolipids elicit various functions in cellular membranes and signal transduction, which may affect cell growth, differentiation, apoptosis, and maintain biological activities. As nutrients, dietary sphingomyelin and its metabolites have wide applications in the food and pharmaceutical industry. In this review, we summarized the distribution, classifications, structures, digestion, absorption and metabolic pathways of sphingolipids, and discussed the nutritional functioning of sphingomyelin in chronic metabolic diseases. The possible implications of dietary sphingomyelin in the modern food preparations including dairy products and infant formula, skin improvement, delivery system and oil organogels are also evaluated. The production of endogenous sphingomyelin is linked to pathological changes in obesity, diabetes, and atherosclerosis. However, dietary supplementations of sphingomyelin and its metabolites have been shown to maintain cholesterol homeostasis and lipid metabolism, and to prevent or treat these diseases. This seemly paradoxical phenomenon shows that dietary sphingomyelin and its metabolites are candidates for food additives and functional food development for the prevention and treatment of chronic metabolic diseases in humans.

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“…These microdomains, often referred to as lipid rafts, are thought to promote select receptor-mediated signaling [ 92 , 93 ]. Hence, SM, by contributing to the homeostasis of these domains, indirectly modulates the activity of some membrane receptors [ 94 , 95 , 96 , 97 ].…”

Section: Introductionmentioning

confidence: 99%

Advancements on the Multifaceted Roles of Sphingolipids in Hematological Malignancies

Raza

Atallah²,

Luberto³

2022

IJMS

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Dysregulation of sphingolipid metabolism plays a complex role in hematological malignancies, beginning with the first historical link between sphingolipids and apoptosis discovered in HL-60 leukemic cells. Numerous manuscripts have reviewed the field including the early discoveries that jumpstarted the studies. Many studies discussed here support a role for sphingolipids, such as ceramide, in combinatorial therapeutic regimens to enhance anti-leukemic effects and reduce resistance to standard therapies. Additionally, inhibitors of specific nodes of the sphingolipid pathway, such as sphingosine kinase inhibitors, significantly reduce leukemic cell survival in various types of leukemias. Acid ceramidase inhibitors have also shown promising results in acute myeloid leukemia. As the field moves rapidly, here we aim to expand the body of literature discussed in previously published reviews by focusing on advances reported in the latter part of the last decade.

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Sphingolipids and Cholesterol

Cited by 15 publications

References 165 publications

Obesity during preclinical Alzheimer's disease development exacerbates brain metabolic decline

Obesity during preclinical Alzheimer's disease development exacerbates brain metabolic decline

The nutritional functions of dietary sphingomyelin and its applications in food

Advancements on the Multifaceted Roles of Sphingolipids in Hematological Malignancies

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