Background And Aims: Resistin has been associated with atherosclerotic inflammation and cardiovascular complications. We and others have previously shown that PKC-epsilon (PKCε) is involved in resistin-induced smooth muscle cell (VSMC) dysfunction at a high pathological concentration. This study aimed to evaluate the role and potential pathways of resistin at a physiological concentration, in atherosclerosis-related inflammation.
Methods: Plasma from patients with atherosclerosis was analyzed for resistin concentration. Patients were divided into tertiles based on resistin levels and cytokines were compared between tertiles. Macrophages were then treated with resistin in the presence or absence of PKCε inhibitor and/or TLR4 blocking-antibody, and their inflammatory state was evaluated with ELISA, RT-PCR, immunocytochemistry, and Western blot.
Results: We observed significant associations between plasma resistin levels and TNF-α, IL-6, IL-12, MIP-1α, MIP-1β, and CD40L. Our in vitro analyses revealed that resistin activated PKCε via TLR4. This was followed by NF-kB activation and induction of a pro-inflammatory phenotype in macrophages, significantly upregulating CD40, downregulating CD206 and stimulating gene expression and secretion of the inflammatory cytokines, for which we found association in our plasma analysis. Resistin also induced persistent TRAM and CD40L upregulation up to 36 h after resistin treatment. PKCε and TLR4 inhibitors suppressed gene expression to levels similar to control, especially when used in combination.
Conclusions: Resistin, at a physiological concentration, exacerbates the inflammatory response of macrophages. PKCε is a key upstream mediator in resistin-induced inflammation that may interact synergistically with TLR4 to promote NF-kB activation, while TRAM is an important signal. PKCε and TRAM may represent novel molecular targets for resistin-associated chronic atherosclerotic inflammation.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5395299 | PMC |
| http://dx.doi.org/10.1016/j.atherosclerosis.2017.02.021 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Low-Frequency Cyclic Stretch Upregulates the Expression of Nuclear Factor Erythroid 2-Related Factor 2 in Human Nucleus Pulposus Cells to Inhibit the Resistin-Induced Interleukin-20 Expression.
JOR Spine
March 2025
Department of Orthopedics, National Cheng Kung University Hospital, College of Medicine National Cheng Kung University Tainan Taiwan.
Background: Resistin may connect obesity and intervertebral disc (IVD) degeneration (IDD) and is linked with chronic inflammation. Furthermore, human IDD is characterized by high expression of interleukin-20 (IL-20). The response of human nucleus pulposus (NP) cells to tensile forces depends on both the duration and magnitude of the force applied.
View Article and Find Full Text PDFVariants in GHRL, RETN, and PLIN1 are associated with obesity, diabetes, and metabolic syndrome, and influence food consumption in adults with obesity.
Nutr Res
December 2024
Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of Sao Paulo, Sao Paulo 05508-000, Brazil. Electronic address:
Genetic and environmental factors have important role in the pathogenesis of obesity and metabolic diseases. We hypothesized that genes involved in energy intake, cellular lipid metabolism and pro-inflammatory adipokines influence obesity-related metabolic disturbances and food intake. We explored the association of GHRL (rs26311G>C and rs4684677A>T), PLIN1 (rs2289487G>A and rs894160G>A), RETN (rs3745367C>T and rs7408174G>A), and NAMPT (rs1319501T>C) variants with obesity, metabolic and inflammatory markers, and food intake composition.
View Article and Find Full Text PDFExercise improves body composition, physical fitness, and blood levels of C-peptide and IGF-1 in 11- to 12-year-old boys with obesity.
Front Physiol
January 2025
Institute of Sports and Arts Convergence, Inha University, Incheon, Republic of Korea.
Introduction: Exercise is vital in preventing and treating obesity. Despite its importance, the understanding of how exercise influences childhood obesity at the biochemical level is limited. In this study, we explore the effects of a 16-week exercise program (EP) on body composition, physical fitness, and the blood levels of hormones related to obesity.
View Article and Find Full Text PDFSerum resistin increases in gestational diabetes but does not differ among various trimesters.
Heliyon
January 2025
Department of Endocrinology, Bangabandhu Sheikh Mujib Medical University, Shahbag, Dhaka, Bangladesh.
Background And Aims: Resistin is inflammatory adipocytokine released from adipose and other tissue. It is thought that it is related to insulin resistance and pathogenesis of gestational diabetes mellitus (GDM). This study was aimed to determine the level of serum resistin in mothers with GDM and normal glucose tolerance (NGT) in all trimesters to see whether it differs among different trimesters as well as between GDM and NGT.
View Article and Find Full Text PDFAdipose tissue may not be a major player in the inflammatory pathogenesis of Autism Spectrum Disorder.
Brain Behav Immun Health
February 2025
Institute of Maternal and Child Medicine, Shenzhen Maternity and Child Healthcare Hospital, Southern Medical University, Shenzhen, China.
Purpose: Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder increasingly recognized for its strong association with chronic inflammation. Adipose tissue functions as an endocrine organ and can secrete inflammatory cytokines to mediate inflammation. However, its involvement in ASD-related inflammation remains unclear.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!