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Lipid environment induces ER stress, TXNIP expression and inflammation in immune cells of individuals with type 2 diabetes

Overview of attention for article published in Diabetologia, October 2017
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  • Good Attention Score compared to outputs of the same age (68th percentile)

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Title
Lipid environment induces ER stress, TXNIP expression and inflammation in immune cells of individuals with type 2 diabetes
Published in
Diabetologia, October 2017
DOI 10.1007/s00125-017-4462-5
Pubmed ID
Authors

Anaïs Szpigel, Isabelle Hainault, Aurélie Carlier, Nicolas Venteclef, Anne-Françoise Batto, Eric Hajduch, Catherine Bernard, Alain Ktorza, Jean-François Gautier, Pascal Ferré, Olivier Bourron, Fabienne Foufelle

Abstract

Obesity and type 2 diabetes are concomitant with low-grade inflammation affecting insulin sensitivity and insulin secretion. Recently, the thioredoxin interacting protein (TXNIP) has been implicated in the activation process of the NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome. In this study, we aim to determine whether the expression of TXNIP is altered in the circulating immune cells of individuals with type 2 vs type 1 diabetes and whether this can be related to specific causes and consequences of inflammation. The expression of TXNIP, inflammatory markers, markers of the unfolded protein response (UPR) to endoplasmic reticulum (ER) stress and enzymes involved in sphingolipid metabolism was quantified by quantitative reverse transcription real-time PCR (qRT-PCR) in peripheral blood mononuclear cells (PBMCs) of 13 non-diabetic individuals, 23 individuals with type 1 diabetes and 81 with type 2 diabetes. A lipidomic analysis on the plasma of 13 non-diabetic individuals, 35 individuals with type 1 diabetes and 94 with type 2 diabetes was performed. The effects of ER stress or of specific lipids on TXNIP and inflammatory marker expression were analysed in human monocyte-derived macrophages (HMDMs) and THP-1 cells. The expression of TXNIP and inflammatory and UPR markers was increased in the PBMCs of individuals with type 2 diabetes when compared with non-diabetic individuals or individuals with type 1 diabetes. TXNIP expression was significantly correlated with plasma fasting glucose, plasma triacylglycerol concentrations and specific UPR markers. Induction of ER stress in THP-1 cells or cultured HMDMs led to increased expression of UPR markers, TXNIP, NLRP3 and IL-1β. Conversely, a chemical chaperone reduced the expression of UPR markers and TXNIP in PBMCs of individuals with type 2 diabetes. The lipidomic plasma analysis revealed an increased concentration of saturated dihydroceramide and sphingomyelin in individuals with type 2 diabetes when compared with non-diabetic individuals and individuals with type 1 diabetes. In addition, the expression of specific enzymes of sphingolipid metabolism, dihydroceramide desaturase 1 and sphingomyelin synthase 1, was increased in the PBMCs of individuals with type 2 diabetes. Palmitate or C2 ceramide induced ER stress in macrophages as well as increased expression of TXNIP, NLRP3 and IL-1β. In individuals with type 2 diabetes, circulating immune cells display an inflammatory phenotype that can be linked to ER stress and TXNIP expression. Immune cell ER stress can in turn be linked to the specific exogenous and endogenous lipid environment found in type 2 diabetes.

X Demographics

X Demographics

The data shown below were collected from the profiles of 9 X users who shared this research output. Click here to find out more about how the information was compiled.
Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 104 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 104 100%

Demographic breakdown

Readers by professional status Count As %
Student > Master 17 16%
Student > Ph. D. Student 13 13%
Researcher 11 11%
Student > Postgraduate 10 10%
Student > Doctoral Student 8 8%
Other 16 15%
Unknown 29 28%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 32 31%
Medicine and Dentistry 9 9%
Agricultural and Biological Sciences 7 7%
Immunology and Microbiology 5 5%
Nursing and Health Professions 3 3%
Other 16 15%
Unknown 32 31%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 4. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 02 February 2018.
All research outputs
#6,390,404
of 23,577,761 outputs
Outputs from Diabetologia
#2,604
of 5,143 outputs
Outputs of similar age
#101,525
of 325,246 outputs
Outputs of similar age from Diabetologia
#85
of 97 outputs
Altmetric has tracked 23,577,761 research outputs across all sources so far. This one has received more attention than most of these and is in the 72nd percentile.
So far Altmetric has tracked 5,143 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 23.3. This one is in the 49th percentile – i.e., 49% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 325,246 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 68% of its contemporaries.
We're also able to compare this research output to 97 others from the same source and published within six weeks on either side of this one. This one is in the 11th percentile – i.e., 11% of its contemporaries scored the same or lower than it.