Cholesterol efflux from THP-1 macrophages is impaired by the fatty acid component from lipoprotein hydrolysis by lipoprotein lipase

Yang, Yanbo; Thyagarajan, Narmadaa; Coady, Breanne M.; Brown, Robert

doi:10.1016/j.bbrc.2014.08.040

Cited by 13 publications

(13 citation statements)

References 36 publications

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“…Lipoprotein lipase (LPL), a lipoprotein hydrolyzing enzyme, contributes to atherogenesis by liberating free fatty acids from lipoproteins [44]. Exposing THP-1 macrophages to LPL-hydrolyzed lipoproteins products led to decreased expression of cholesterol transporter genes including ATP-binding cassette transporters, peroxisome proliferator-activated receptors (PPARs), HDL scavenger receptor and liver x receptor.…”

Section: Adipokinesmentioning

confidence: 99%

Non-traditional cytokines: How catecholamines and adipokines influence macrophages in immunity, metabolism and the central nervous system

2015

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Catecholamines and adipokines function as hormones; catecholamines as neurotransmitters in the sympathetic nervous system, and adipokines as mediators of metabolic processes. It has become increasingly clear, however, that both also function as immunomodulators of innate and adaptive immune cells, including macrophages. Macrophages can respond to, as well as produce their own catecholamines. Dopamine, noradrenaline, and adrenaline are the most abundant catecholamines in the body, and can induce both pro-inflammatory and anti-inflammatory immune responses in macrophages, as well as non-immune processes such as thermogenesis. Though they are responsive to adipokines, particularly lipoproteins, leptin, and adiponectin, macrophages generally do synthesize their own adipokines, with the exception being resistin-like molecules. Adipokines contribute to adverse metabolic and immune response by stimulating lipid accumulation, foam cell formation and pro-inflammatory cytokine production in macrophages. Adipokines can also promote balance or resolution during metabolic and immune processes by promoting reverse lipid transport and expression of Th2 cytokines. This review will explore the mechanisms by which catecholamines and adipokines influence macrophage function in neural pathways, immunity and metabolism.

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Section: Adipokinesmentioning

confidence: 99%

Non-traditional cytokines: How catecholamines and adipokines influence macrophages in immunity, metabolism and the central nervous system

2015

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“…44 Macrophage-derived LPL and its associated lipolysis product were shown to decrease expression of ABCA1 and ABCG1, resulting in reduced cholesterol efflux from cells. 45 Conversely, downregulation of LPL expression in THP-1 macrophages increased ABCA1 expression and cholesterol efflux from cells. 46 Thus, the net result of silencing of HDAC9 induced by miR-182 is to block cholesterol efflux from macrophages.…”

Section: Effects Of Mir-182 On Proinflammatory Cytokines and Lipids Imentioning

confidence: 99%

MicroRNA-182 Promotes Lipoprotein Lipase Expression and Atherogenesisby Targeting Histone Deacetylase 9 in Apolipoprotein E-Knockout Mice

Cheng

Gong

Zhao

et al. 2017

Circ J

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“…Because the MUFA component of the total FFA mixture, and specifically palmitoleate, resulted in the significant phosphorylation of Akt, we examined if palmitoleate would indeed alter the levels of select species of PIPx within THP-1 macrophages over an 18 hour period. We chose this time period because we previously showed it was a sufficient period for the total FFA to impair cholesterol efflux [21]. No significant changes were observed for all assessed species of phosphatidylinositol (PI)-(34:1, 36:0, 36:1, 36:2, 38:3, and 38:4) ( Fig 3A), and for all assessed species of phosphatidylinositol monophosphate (PIP)-(36:1, 36:2, 38:3, and 38:4) ( Fig 3B).…”

Section: Resultsmentioning

confidence: 99%

“…We have also previously shown that the hydrolysis products liberated from total lipoproteins by LPL, and notably the total FFA component, impaired the gene expression of the cholesterol efflux transporters ATP binding cassette transporter A1 (ABCA1), ATP binding cassette transporter G1 (ABCG1), and scavenger receptor BI (SR-BI) within THP-1 macrophages after 18 hours [21]; in addition, cholesterol efflux to apolipoprotein A-I (apoA-I) was impaired [21]. Because the total FFA component of lipoprotein hydrolysis products generated by LPL increases the levels of phosphorylated Akt (pAkt) [16] and it inhibits cholesterol efflux [21], and the inhibition of Akt improves cholesterol efflux [20], we suspected that Akt was a key intermediate in the mechanism by which LPL impairs cholesterol efflux. Thus, we hypothesized that one or more specific fatty acids that exist within the total FFA component of lipoprotein hydrolysis products that are generated by LPL impair cholesterol efflux through the activation of Akt.…”

Section: Introductionmentioning

confidence: 97%

THP-1 macrophage cholesterol efflux is impaired by palmitoleate through Akt activation

et al. 2020

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Lipoprotein lipase (LPL) is upregulated in atherosclerotic lesions and it may promote the progression of atherosclerosis, but the mechanisms behind this process are not completely understood. We previously showed that the phosphorylation of Akt within THP-1 macrophages is increased in response to the lipid hydrolysis products generated by LPL from total lipoproteins. Notably, the free fatty acid (FFA) component was responsible for this effect. In the present study, we aimed to reveal more detail as to how the FFA component may affect Akt signalling. We show that the phosphorylation of Akt within THP-1 macrophages increases with total FFA concentration and that phosphorylation is elevated up to 18 hours. We further show that specifically the palmitoleate component of the total FFA affects Akt phosphorylation. This is tied with changes to the levels of select molecular species of phosphoinositides. We further show that the total FFA component, and specifically palmitoleate, reduces apolipoprotein A-I-mediated cholesterol efflux, and that the reduction can be reversed in the presence of the Akt inhibitor MK-2206. Overall, our data support a negative role for the FFA component of lipoprotein hydrolysis products generated by LPL, by impairing macrophage cholesterol efflux via Akt activation.

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Cholesterol efflux from THP-1 macrophages is impaired by the fatty acid component from lipoprotein hydrolysis by lipoprotein lipase

Cited by 13 publications

References 36 publications

Non-traditional cytokines: How catecholamines and adipokines influence macrophages in immunity, metabolism and the central nervous system

Non-traditional cytokines: How catecholamines and adipokines influence macrophages in immunity, metabolism and the central nervous system

MicroRNA-182 Promotes Lipoprotein Lipase Expression and Atherogenesisby Targeting Histone Deacetylase 9 in Apolipoprotein E-Knockout Mice

THP-1 macrophage cholesterol efflux is impaired by palmitoleate through Akt activation

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