Role of lipids in the metabolism and activation of immune cells

Hubler, Merla J.; Kennedy, Arion

doi:10.1016/j.jnutbio.2015.11.002

Cited by 189 publications

(150 citation statements)

References 87 publications

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“…Similarly, short chain fatty acids have been shown to enhance Teff‐cell differentiation and cytokine production, via activation of mTOR, in a context‐dependent manner . Conversely, the polyunsaturated fatty acids docosahexaenoic acid (DHA) and alpha‐linoleic acid have been shown to increase secretion of the anti‐inflammatory T‐cell cytokine IL‐10, decrease pro‐inflammatory cytokine production, and impair T‐cell proliferation . The exact mechanism by which fatty acids regulate T‐cell metabolism in obesity requires further investigation.…”

Section: T‐cell Metabolism and Adipokines In Obesitymentioning

confidence: 99%

Nutritional effects on T‐cell immunometabolism

2017

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T cells are highly influenced by nutrient uptake from their environment, and changes in overall nutritional status, such as malnutrition or obesity, can result in altered T-cell metabolism and behavior. In states of severe malnutrition or starvation, T-cell survival, proliferation, and inflammatory cytokine production are all decreased, as is T-cell glucose uptake and metabolism. The altered T-cell function and metabolism seen in malnutrition is associated with altered adipokine levels, most particularly decreased leptin. Circulating leptin levels are low in malnutrition, and leptin has been shown to be a key link between nutrition and immunity. The current view is that leptin signaling is required to upregulate activated T-cell glucose metabolism and thereby fuel T-cell activation. In the setting of obesity, T cells have been found to have a key role in promoting the recruitment of inflammatory macrophages to adipose depots along with the production of inflammatory cytokines that promote the development of insulin resistance leading to diabetes. Deletion of T cells, key T-cell transcription factors, or pro-inflammatory T-cell cytokines prevents insulin resistance in obesity and underscores the importance of T cells in obesity-associated inflammation and metabolic disease. Altogether, T cells have a critical role in nutritional immunometabolism.

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Section: T‐cell Metabolism and Adipokines In Obesitymentioning

confidence: 99%

Nutritional effects on T‐cell immunometabolism

2017

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“…Inflammation-mediated insulin resistance might be beneficial for fueling immunity against acute bacterial infection, but becomes pathological when ‘sterile’ chronic low-grade inflammation is induced by obesity and other non-infectious origins [150]. In addition, immune modulation leading to Th-2 polarization may directly affect lipids and their metabolism [151]. For example, the redirection of lipids to immune function may result in lower accumulation of self-antigens against LDL and byproducts in the lumen and less immune activity directed towards those antigens.…”

Section: Cardio-metabolic Protective Effects Of Helminth Infectionmentioning

confidence: 99%

Cardiovascular disease and type 2 diabetes in evolutionary perspective: A critical role for helminths?

Gurven

Trumble

Stieglitz

et al. 2016

EMPH

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Heart disease and type 2 diabetes are commonly believed to be rare among contemporary subsistence-level human populations, and by extension prehistoric populations. Although some caveats remain, evidence shows these diseases to be unusual among well-studied hunter-gatherers and other subsistence populations with minimal access to healthcare. Here we expand on a relatively new proposal for why these and other populations may not show major signs of these diseases. Chronic infections, especially helminths, may offer protection against heart disease and diabetes through direct and indirect pathways. As part of a strategy to insure their own survival and reproduction, helminths exert multiple cardio-protective effects on their host through their effects on immune function and blood lipid metabolism. Helminths consume blood lipids and glucose, alter lipid metabolism, and modulate immune function towards Th-2 polarization—which combined can lower blood cholesterol, reduce obesity, increase insulin sensitivity, decrease atheroma progression, and reduce likelihood of atherosclerotic plaque rupture. Traditional cardiometabolic risk factors, coupled with the mismatch between our evolved immune systems and modern, hygienic environments may interact in complex ways. In this review, we survey existing studies in the non-human animal and human literature, highlight unresolved questions and suggest future directions to explore the role of helminths in the etiology of cardio-metabolic disease.

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“…Of note c-Src activation is a key event to c-Jun N-terminal kinase (JNK) activation, and the latter can be induced by saturated FA but not by PUFA [11]. We suggest review articles on the effects of FAs on immune cells [12][13][14].…”

Section: Introductionmentioning

confidence: 95%

Cholesterol and saturated fatty acid stabilize dimerization of helical transmembrane peptides by lowering energy cost related to peptides desolvation from lipids upon dimerization: an insight from atomistic simulation

Nishizawa¹,

Nishizawa²

2017

Biomed Res Clin Prac

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Lipids composition of cellular membrane is known to be crucial for regulations of activities of many cells. In immune cells, activities of diverse receptors including T cell receptors and innate immunity receptors are modulated by lipids. In the presence of cholesterol in membranes, saturated fatty acids (FAs) promote formation of ordered lipid microdomain formation and enhance receptor-mediated signaling and inflammation, but the mechanistic detail for the effects of saturated FAs has not been well understood. Here we show that, for a poly-Ile transmembrane (TM) helical peptide, a self-dimerized state is stabilized by about -2.2 kJ/mol by the lipid bilayer of 1:1:1 palmitoyloleoylphosphatidylcholine (POPC)/dipalmitoylphosphatidylcholine (DPPC)/cholesterol compared to a pure dioleoylphosphatidylcholine (DOPC) bilayer in molecular simulations with a united-atom force field. Energy decomposition analysis suggested that the DOPC bilayer has a high Lennard-Jones (LJ) potential energy cost due to non-optimal protein-lipid interactions (poor fitting) upon peptide dimerization relative to the monomers state, but the 1:1:1 bilayer showed a relatively small differential of the protein-lipid LJ potential between the dimer and monomer states. In the 1:1:1 bilayer, both POPC and DPPC resided near the dimerized peptides, with cholesterol mostly residing >3 Å distant from peptides surface. However, a potential energy decomposition analysis did not support the view that peptides segregation from the cholesterol-rich sub-compartment is important for stabilizing the dimerization. Rather, peptide solvation by phospholipids preserved relatively well even after dimerization possibly due to the straightened acyl chains was the key for the dimer stabilization. Taken together, saturated FAs of phospholipids and cholesterol appear to stabilize transmembrane helical peptide dimerization in a sequence-nonspecific manner through the ability of such lipids to indirectly assist peptides solvation by lipids after peptide dimerization.

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Role of lipids in the metabolism and activation of immune cells

Cited by 189 publications

References 87 publications

Nutritional effects on T‐cell immunometabolism

Nutritional effects on T‐cell immunometabolism

Cardiovascular disease and type 2 diabetes in evolutionary perspective: A critical role for helminths?

Cholesterol and saturated fatty acid stabilize dimerization of helical transmembrane peptides by lowering energy cost related to peptides desolvation from lipids upon dimerization: an insight from atomistic simulation

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