Palmitate-induced inflammatory pathways in human adipose microvascular endothelial cells promote monocyte adhesion and impair insulin transcytosis

Pillon, Nicolas; Azizi, Paymon; Li, Yujin E.; Liu, Jun; Wang, Changsen; Chan, Kenny L.; Hopperton, Kathryn E.; Bazinet, Richard P.; Heit, Bryan; Bilan, Philip J.; Lee, Warren L.; Klip, Amira

doi:10.1152/ajpendo.00611.2014

Cited by 64 publications

(55 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…71, 72, 73 Briefly, 90–120 min time-lapse videos were captured of macrophages ectopically expressing the plasmalamellar marker PM-RFP, GFP-tagged Rab17 and far-red-labeled targets for phagocytosis/efferocytosis. TIFF stacks of individual cells were then exported and a local threshold applied to the target channel using a local neighborhood 2 × the size of the targets.…”

Section: Methodsmentioning

confidence: 99%

Rab17 mediates differential antigen sorting following efferocytosis and phagocytosis

et al. 2016

Self Cite

View full text Add to dashboard Cite

Macrophages engulf and destroy pathogens (phagocytosis) and apoptotic cells (efferocytosis), and can subsequently initiate adaptive immune responses by presenting antigens derived from engulfed materials. Both phagocytosis and efferocytosis share a common degradative pathway in which the target is engulfed into a membrane-bound vesicle, respectively, termed the phagosome and efferosome, where they are degraded by sequential fusion with endosomes and lysosomes. Despite this shared maturation pathway, macrophages are immunogenic following phagocytosis but not efferocytosis, indicating that differential processing or trafficking of antigens must occur. Mass spectrometry and immunofluorescence microscopy of efferosomes and phagosomes in macrophages demonstrated that efferosomes lacked the proteins required for antigen presentation and instead recruited the recycling regulator Rab17. As a result, degraded materials from efferosomes bypassed the MHC class II loading compartment via the recycling endosome – a process not observed in phagosomes. Combined, these results indicate that macrophages prevent presentation of apoptotic cell-derived antigens by preferentially trafficking efferocytosed, but not phagocytosed, materials away from the MHC class II loading compartment via the recycling endosome pathway.

show abstract

Section: Methodsmentioning

confidence: 99%

Rab17 mediates differential antigen sorting following efferocytosis and phagocytosis

et al. 2016

Self Cite

View full text Add to dashboard Cite

show abstract

“…High glucose conditions induce the overexpression of TLRs, such as TLR2 and TLR4 in endothelial cells in adipose tissue 72,133 , the retina 134 , coronary arteries 40 , and kidney tissues 135 . Endothelial cells exposed to fluctuating glucose concentrations induce an upregulation of TLR4 and TLR2 expression and this process has been associated with increased NFκB, IL8, MCP-1, ICAM-1, and VCAM-1 (Figure 3).…”

Section: [H2] Involvement Of Tlrsmentioning

confidence: 99%

Innate immunity in diabetes and diabetic nephropathy

2015

View full text Add to dashboard Cite

Abstract:The innate immune system consists of several classes of pattern recognition receptors (PRRs), including membrane-bound Toll-like receptors (TLRs) and nucleotide-binding domain leucine-rich oligomerization domain (NOD)-like receptors (NLRs).These receptors detect pathogen-associated molecular patterns (PAMPs) and danger-associated molecular patterns (DAMPs) in the extracellular and intracellular space. Intracellular NLRs constitute inflammasomes, which activate and release caspase-1, IL1β, and IL18 and thus initiate an inflammatory response. Systemic and local low-grade inflammation and release of proinflammatory cytokines are implicated in the development and progression of diabetes mellitus and diabetic nephropathy. TLR2, TLR4, and the NLRP3 inflammasome are critically involved in the inflammatory responses in pancreatic islets, adipose, liver and kidney tissues. This Review discusses how innate immune system-driven inflammatory processes can lead to apoptosis, tissue fibrosis, and organ dysfunction to cause insulin resistance, impaired insulin secretion, and renal failure. We propose that careful targeting of TLR2, TLR4, and NLRP3 signalling pathways may be beneficial for the treatment of diabetes mellitus and diabetic nephropathy. 2 Key points The innate immune system consists of several classes of pattern recognition receptors, including TLRs and NLRs, which detect pathogen-associated and danger-associated molecular patterns and initiate an inflammatory response  TLR2 and TLR4 are the predominant toll-like receptors expressed on pancreatic β cells that trigger an inflammatory response in insulitis during type 1 diabetes mellitus  TLR2 and TLR4 signaling, and activation of NLRP3 inflammasomes results in production of various proinflammatory cytokines that can induce insulin resistance in type 2 diabetes mellitus (T2DM) and obesity  Innate immune responses in T2DM and obesity are modulated by the status of the gut microbiota, autophagy, and adipokines  TLR2, TLR4, NOD2, and NLRP3 inflammasome-mediated inflammation are involved in the perpetuation of inflammation in diabetic nephropathy  The activation of TLRs and NLRs stimulates the expression of MCP-1, which is associated with the progression of diabetic nephropathy [H1] IntroductionThe prevalence of diabetes mellitus is estimated to be 8.3%, affecting ~387 million people as of 2014. The number of patients living with diabetes mellitus is expected to increase to ~592 million by 2035, as reported by the International Diabetes Federation 1 . The incidence of end-stage renal disease (ESRD) is also rapidly increasing worldwide but varies up to 15-fold by country. In 2012, the number of new diagnoses of ESRD worldwide ranged from 25 to 467 patients per million. The proportion of new cases of ESRD with diabetes mellitus as the primary cause also differs by country, with 66% cases reported in Singapore and 12-16% cases reported in Ukraine, Romania, and the Netherlands 2 . Although intensified multifactorial intervention in patients with type 2 diabete...

show abstract

“…Saturated fatty acids trigger proinflammatory signaling pathways (11). For example, palmitic acid activated toll-like receptor 4 (TLR4), leading to nuclear transcription factor κB (NF-κB) signaling and increased gene expression of IL-6, IL-8, vascular cell adhesion molecule-1 (VCAM-1), and intercellular adhesion molecule-1 (ICAM-1) in contrast, the monounsaturated palmioleate did not have inflammatory sequelae (11).…”

Section: Introductionmentioning

confidence: 99%

“…For example, palmitic acid activated toll-like receptor 4 (TLR4), leading to nuclear transcription factor κB (NF-κB) signaling and increased gene expression of IL-6, IL-8, vascular cell adhesion molecule-1 (VCAM-1), and intercellular adhesion molecule-1 (ICAM-1) in contrast, the monounsaturated palmioleate did not have inflammatory sequelae (11). A meal made with butter, a rich source of saturated fatty acids, activated NF-κB in peripheral blood mononuclear cells and also increased sICAM-1 concentrations, but a meal with olive oil, a rich source of oleic acid, did not (12).…”

Section: Introductionmentioning

confidence: 99%

Depression, daily stressors and inflammatory responses to high-fat meals: when stress overrides healthier food choices

et al. 2016

View full text Add to dashboard Cite

Depression, stress, and diet can all alter inflammation. This double-blind, randomized crossover study addressed the impact of daily stressors and a history of major depressive disorder (MDD) on inflammatory responses to high-fat meals. During two separate 9.5 hour admissions, 58 healthy women (38 breast cancer survivors and 20 demographically-similar controls), mean age 53.1 years, received either a high saturated fat meal or a high oleic sunflower oil meal. The Daily Inventory of Stressful Events assessed prior day stressors and the Structured Clinical Interview for DSM-IV evaluated MDD. As expected, for a woman with no prior day stressors, C-reactive protein (CRP), serum amyloid A (SAA), intercellular adhesion molecule-1 (sICAM-1), and vascular cell adhesion molecule-1 (sVCAM-1) were higher following the saturated fat meal than the high oleic sunflower oil meal after controlling for pre-meal measures, age, trunk fat, and physical activity. But if a woman had prior day stressors, these meal-related differences disappeared – because the stressors heightened CRP, SAA, sICAM-1, and sVCAM-1 responses to the sunflower oil meal, making it look more like the responses to the saturated fat meal. In addition, women with an MDD history had higher post-meal blood pressure responses than those without a similar history. These data show how recent stressors and an MDD history can reverberate through metabolic alterations, promoting inflammatory and atherogenic responses.

show abstract

Palmitate-induced inflammatory pathways in human adipose microvascular endothelial cells promote monocyte adhesion and impair insulin transcytosis

Abstract: -induced inflammatory pathways in human adipose microvascular endothelial cells promote monocyte adhesion and impair insulin transcytosis.

Cited by 64 publications

References 51 publications

Rab17 mediates differential antigen sorting following efferocytosis and phagocytosis

Rab17 mediates differential antigen sorting following efferocytosis and phagocytosis

Innate immunity in diabetes and diabetic nephropathy

Depression, daily stressors and inflammatory responses to high-fat meals: when stress overrides healthier food choices

Contact Info

Product

Resources

About