Regulation of intestinal lipid metabolism: current concepts and relevance to disease

Ko, Chih‐Wei; Qu, Jie; Black, Dennis D.; Tso, Patrick

doi:10.1038/s41575-019-0250-7

Cited by 286 publications

(219 citation statements)

References 199 publications

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“…These findings have been corroborated by experiments conducted in human intestinal organoids, which show high expression of SARS-CoV-2 entry factors and infection of human enterocytes with both SARS-CoV and SARS-CoV-2 (Lamers et al, 2020). Enterocytes are highly secretory cells which express ACE2 and produce large lipid vesicles containing lipoproteins involved in the generation of chylomicrons, trygliceride-rich lipoprotein particles important for systemic lipid transfer (Ko et al, 2020).…”

Section: Introductionmentioning

confidence: 63%

SARS-CoV-2 infects brain choroid plexus and disrupts the blood-CSF-barrier

Pellegrini

Albecka

Mallery

et al. 2020

Preprint

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Coronavirus disease-19 (COVID-19), caused by the SARS-CoV-2 virus, leads primarily to respiratory symptoms that can be fatal, particularly in at risk individuals. However, neurological symptoms have also been observed in patients, including headache, seizures, stroke, and fatigue. The cause of these complications is not yet known, and whether they are due to a direct infection of neural cells, such as neurons and astrocytes, or through indirect effects on supportive brain cells, is unknown. Here, we use brain organoids to examine SARS-CoV-2 neurotropism. We examine expression of the key viral receptor ACE2 in single-cell RNA sequencing (scRNA-seq) revealing that only a subset of choroid plexus cells but not neurons or neural progenitors express this entry factor. We then challenge organoids with both SARS-CoV-2 spike protein pseudovirus and live virus to demonstrate high viral tropism for choroid plexus epithelial cells but not stromal cells, and little to no infection of neurons or glia. We find that infected cells of the choroid plexus are an apolipoprotein and ACE2 expressing subset of epithelial barrier cells. Finally, we show that infection with live SARS-CoV-2 leads to barrier breakdown of the choroid plexus. These findings suggest that neurological complications may result from effects on the choroid plexus, an important barrier that normally prevents entry of immune cells and cytokines into the cerebrospinal fluid (CSF) and brain.

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Section: Introductionmentioning

confidence: 63%

SARS-CoV-2 infects brain choroid plexus and disrupts the blood-CSF-barrier

Pellegrini

Albecka

Mallery

et al. 2020

Preprint

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“…Apolipoproteins, including apolipoprotein A (ApoA), apolipoprotein B (ApoB), apolipoprotein C (ApoC) and microsomal triglyceride transfer protein (MTP), play important roles during this process. Triacylglycerol (TG) and nonesterified fatty acid (NEFA) are packaged into large, spherical CMs and secreted into the lymphatic system; this process mainly relies on the activity of MTP and ApoB[ 5 , 6 ]. However, in addition to CMs, cholesterol can be secreted in HDL.…”

Section: Introductionmentioning

confidence: 99%

“…However, in addition to CMs, cholesterol can be secreted in HDL. In HDL, MTP showed no effect on the secretion of cholesterol, while the deficiency of ApoA1 can specifically decrease the quantities of cholesterol secreted with HDL[ 5 , 7 ]. The improvement of lipid metabolism helps to inhibit the progress of NAFLD.…”

Section: Introductionmentioning

confidence: 99%

Acupuncture improved lipid metabolism by regulating intestinal absorption in mice

Guo

Meng

et al. 2020

WJG

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BACKGROUND Non-alcoholic fatty liver disease (NAFLD), in which abnormal lipid metabolism plays an important role in disease progression, has become a pandemic. Abnormal lipid metabolism, for example an increased fat intake, has been thought to be an initial factor leading to NAFLD. The small intestine is the main site of dietary lipid absorption. A number of clinical trials have shown that acupuncture has positive effects in the regulation of lipid metabolism, which is closely associated with the progression of NAFLD. We therefore hypothesized that, acupuncture can improve the conditions of NAFLD by regulating intestinal absorption of lipid. AIM To study the role of acupuncture treatment in the improvement of metabolic syndrome secondary to NAFLD by mouse model. METHODS 8-wk-old male C57BL/6J mice were fed a methionine- and choline-deficient diet for 3 wk. Then, all mice were separated randomly into acupoints group (AG) or non-acupoints group (NG) with high fat diet feeding. Needling treatment was performed at Zu san li, Guan yuan and Yong quan acupoints as acupuncture treatment to AG mice while non-acupoints place to NG mice. Finally, mice were anesthetized with an injection of ketamine-medetomidine and euthanized by exsanguination. RESULTS An apparent improvement of obesity was found in AG mice after acupuncture treatment. In AG mice, the body weight was much lower (22.6 ± 1.2 g vs 28.1 ± 1.0 g, P < 0.005) in comparison to NG mice. The length of small intestine in AG mice was significantly shorter (26.7 ± 2.3 cm vs 32.7 ± 2.7 cm, P < 0.005). A large amount of chyme was observed in the lumen of the AG small intestine. The expression of microsomal triglyceride transfer protein, apolipoprotein B and apolipoprotein C2 was downregulated. Triacylglycerols (TGs), total cholesterol and nonesterified fatty acid (NEFA) levels of the small intestinal tissue were significantly higher in AG mice, but the serum TGs and NEFA levels were reduced in AG mice. CONCLUSION These results indicate that acupuncture at Zu san li, Guan yuan and Yong quan suppressed lipid absorption by downregulating the expression of apolipoproteins in the small intestine.

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“…Lipid metabolism is essential for providing many cell types with an adequate supply of energy (Fig. 1) [62]. FA are a subgroup of lipids that have been implicated in human and murine Treg differentiation, survival, and function, although the exact contribution of the different lipids in both Treg population remain to be addressed [15,55,63].…”

Section: Overview Of Metabolic Control In Treg Cellsmentioning

confidence: 99%

Regulatory T cell metabolism at the intersection between autoimmune diseases and cancer

2020

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Regulatory T cells (Tregs) are critical for peripheral immune tolerance and homeostasis, and altered Treg behavior is involved in many pathologies, including autoimmunity and cancer. The expression of the transcription factor FoxP3 in Tregs is fundamental to maintaining their stability and immunosuppressive function. Recent studies have highlighted the crucial role that metabolic reprogramming plays in controlling Treg plasticity, stability, and function. In this review, we summarize how the availability and use of various nutrients and metabolites influence Treg metabolic pathways and activity. We also discuss how Treg‐intrinsic metabolic programs define and shape their differentiation, FoxP3 expression, and suppressive capacity. Lastly, we explore how manipulating the regulation of Treg metabolism might be exploited in different disease settings to achieve novel immunotherapies.

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Regulation of intestinal lipid metabolism: current concepts and relevance to disease

Cited by 286 publications

References 199 publications

SARS-CoV-2 infects brain choroid plexus and disrupts the blood-CSF-barrier

SARS-CoV-2 infects brain choroid plexus and disrupts the blood-CSF-barrier

Acupuncture improved lipid metabolism by regulating intestinal absorption in mice

Regulatory T cell metabolism at the intersection between autoimmune diseases and cancer

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