One-week high-fat diet leads to reduced toll-like receptor 2 expression and function in young healthy men

Wan, Zhongxiao; Durrer, Cody; Mah, Dorrian; Simtchouk, Svetlana; Little, Jonathan P.

doi:10.1016/j.nutres.2014.08.012

Cited by 15 publications

(14 citation statements)

References 25 publications

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“…Although TLR2 is implicated in the inflammatory response in high-fat diet (HFD)-induced obesity in rodents and in human gene expression studies 55 , saturated and polyunsaturated fatty acids did not elicit proinflammatory effects in human adipose tissue and primary adipocyte culture 56 . Conversely, administration of a HFD for 1 week to healthy males reduced the expression of TLR2 57 . Such discrepancies between animal and human investigations complicate the understanding of the molecular mechanisms underlying T2DM and obesity, and further clinical trials are required to confirm the benefits of inhibiting TLR2 signaling in patients.…”

Section: [H3] Tlr2 and Tlr4mentioning

confidence: 95%

Innate immunity in diabetes and diabetic nephropathy

2015

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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...

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Section: [H3] Tlr2 and Tlr4mentioning

confidence: 95%

Innate immunity in diabetes and diabetic nephropathy

2015

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“…Whole blood was diluted 1 : 10 with serum-free RPMI-1640 medium (penicillin 100 U/mL, streptomycin 100 μ g/mL) (i.e., 540 μ L whole blood diluted in 4.86 mL RPMI-1640 medium), plated in duplicate on 24-well plates at a final volume of 600 μ L, and cultured at 37°C in a humidified incubator (5% CO 2 ) as described by Wan et al [ 28 ]. Samples were stimulated with the TLR4 agonist LPS (1, 10 ng/mL) and TLR2 agonist Pam3Cys-SK4 [ 29 ] (1, 10 ng/mL) and supernatants were harvested after 24 h via centrifuge at 2000 g for 15 min at 4°C.…”

Section: Methodsmentioning

confidence: 99%

“…PBMCs were isolated by gradient density centrifugation of peripheral blood using Ficoll-Paque Plus as described previously by our laboratory [ 28 ]. Briefly, 5 mL of blood was layered onto 5 mL of Ficoll-Paque Plus in a sterile 15 mL tube and was centrifuged for 15 min at 800 g and at 20°C.…”

Section: Methodsmentioning

confidence: 99%

Effects of 8-Week Hatha Yoga Training on Metabolic and Inflammatory Markers in Healthy, Female Chinese Subjects: A Randomized Clinical Trial

Chen

Xia

Qin

et al. 2016

BioMed Research International

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We aimed to determine the effects of an 8 wk Hatha yoga training on blood glucose, insulin, lipid profiles, endothelial microparticles (EMPs), and inflammatory status in healthy, lean, and female Chinese subjects. A total of 30 healthy, female Chinese subjects were recruited and randomized into control or yoga practice group. The yoga practice included 8 wks of yoga practice (2 times/wk) for a total of 16 times. Fasting blood samples were collected before and after yoga training. Plasma was isolated for the measurement of lipid profiles, glucose, insulin, EMPs, and inflammatory cytokines. Whole blood was cultured ex vivo and stimulated with lipopolysaccharide (LPS) and Pam3Cys-SK4. Peripheral blood mononuclear cells (PBMCs) were isolated for the measurement of TLR2 and TLR4 protein expression. Yoga practice significantly reduced plasma cholesterol, LDL-cholesterol, insulin levels, and CD31+/CD42b− EMPs. Cultured whole blood from the yoga group has reduced proinflammatory cytokines secretion both at unstimulated condition and when stimulated with Pam3Cys-SK4; this might be associated with reduced TLR2 protein expression in PBMCs after yoga training. Hatha yoga practice in healthy Chinese female subjects could improve hallmarks related to MetS; thus it can be considered as an ancillary intervention in the primary MetS prevention for the healthy population. This trial is registered with ChiCTR-IOR-14005747.

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“…High-fat diet TLR2 and TLR4 have been involved in inflammatory responses to high-fat diet (HFD)-induced obesity in rats (Wan et al 2014;Lee et al 2015). HFD resulted in decreased TLR2 and 4 expression on CD14 monocytes and impaired their function which was detected by the increased secretion of IL-1β, IL-6, and TNF-α from PBMCs in human (Wan et al 2014). HFD induced TLR4-dependent macrophage cell activation with significant increase in NF-κB and IL-6 (Lee et al 2015).…”

Section: Processed Food Containing Microbial Stimulantsmentioning

confidence: 99%

Micronutrients and many important factors that affect the physiological functions of toll-like receptors

2019

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Background: Toll-like receptors (TLRs) are type I integral transmembrane receptors involved in recognition and conveying of pathogens to the immune system. These receptors are located either on cell surfaces or within endosomes. They are activated by specific ligand leading to the release of cytokines via signal transduction pathway. The excess production of these cytokines leads to disrupt the immune homeostasis. There are several factors regulating TLR expression and consequently affecting their functions. Among these are inflammation, cytokines, some cellular process, air pollution, depression, stress, some drugs, genetic polymorphism, nutrition, and micronutrients. Some micronutrients (vitamins and trace elements) may be considered as important TLR regulators, as they have immunomodulatory functions. Vitamins D, B12, and A; zinc; copper; and iron have important role on innate immune responses. Aim of work: This review gives a brief idea on TLR family and attempts to cover the factors affecting the physiological functions of them. Conclusion: Of many factors affecting TLRs functions are micronutrients. There is a shortage of researches concerning the effect of micronutrients deficiency on the function of TLRs, all of which focused on vitamin D but other vitamins have not got the same importance that they deserve. This orients our efforts to work at this point in the future.

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One-week high-fat diet leads to reduced toll-like receptor 2 expression and function in young healthy men

Cited by 15 publications

References 25 publications

Innate immunity in diabetes and diabetic nephropathy

Innate immunity in diabetes and diabetic nephropathy

Effects of 8-Week Hatha Yoga Training on Metabolic and Inflammatory Markers in Healthy, Female Chinese Subjects: A Randomized Clinical Trial

Micronutrients and many important factors that affect the physiological functions of toll-like receptors

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