Age-Dependent Changes of Adipokine and Cytokine Secretion From Rat Adipose Tissue by Endogenous and Exogenous Toll-Like Receptor Agonists

Abstract

White adipose tissue but recently also brown adipose tissue have emerged as endocrine organs. Age-associated obesity is accompanied by prolonged and elevated lipopolysaccharide (LPS)-induced sickness symptoms and increased cytokine and adipokine levels in the circulation partially originating from adipose tissue. In the present study, ex vivo fat explants were used to investigate how the exogenous pathogen-associated molecular pattern (PAMP) LPS or the endogenous danger-associated molecular patterns (DAMPs) high mobility group box-1 protein (HMGB1) and biglycan modulate the release of cytokines and adipokines/batokines and, thus, could influence systemic and/or local inflammation. The response of adipose tissue (epididymal, retroperitoneal, subcutaneous, and brown) was compared between young lean and old obese rats (2 vs. 24 months old). LPS induced a strong interleukin (IL)-6 and tumor necrosis factor (TNF) alpha release into the supernatant of all adipose tissue types investigated. HMGB1 (subcutaneous) and biglycan (retroperitoneal) led to an increased release of IL-6 and TNFalpha (HMGB1) and decreased visfatin and adiponectin (biglycan) secretion from epididymal adipose tissue (young rats). Visfatin was also decreased by HMGB1 in retroperitoneal adipose tissue of old rats. We found significantly higher leptin (all fat pads) and adiponectin (subcutaneous) levels in supernatants of adipose tissue from old compared to young rats, whereas visfatin secretion showed the opposite. The expression of the biglycan receptor Toll-like receptor (TLR) 2 as well as the LPS and HMGB1 receptors TLR4 and receptor for advanced glycation end products (RAGE) were reduced with age (TLR4/RAGE) and by stimulation with their ligands (subcutaneous). Overall, we revealed that adipokines/adipose-tissue released cytokines show some modulation of their release caused by mediators of septic (batokines) and Peek et al. Age-Dependent Adipokine and Cytokine Secretion sterile inflammation with potential implication for acute and chronic disease. Moreover, aging may increase or decrease the release of fat-derived mediators. These data show that DAMPS and LPS locally modulate cytokine secretion while only DAMPS but not LPS can locally alter adipokine secretion during inflammation.

Bioinformatics-Led Discovery of Osteoarthritis Biomarkers and Inflammatory Infiltrates

“…In osteoarthritis and other inflammatory disorders, fat pads contribute to the generation of adipokines and cytokines. This study and a previous study ( 57 ) demonstrated that adipokines regulate osteoarthritis and bone remodeling. This study’s GSEA analysis revealed that osteoarthritis was linked to graft-versus-host disease and Leishmania protozoa infection, which was one of the study’s findings.…”

Tlr2/4 Double Knockout Attenuates the Degeneration of Primary Auditory Neurons: Potential Mechanisms From Transcriptomic Perspectives

“…The analysis of PPI interactions indicated six key modules ( Table 1 ), and 10 molecules were the most significant, including COMP, COL1A1, STAT3, HAPLN1, HBEGF, CCL2, MMP13, SMAD4, CXCL1, and CTSK. We noticed that these enriched activities of immune responses, TNF signaling pathway, and cytokine-cytokine receptor interaction could be regulated by Tlr molecules ( Peek et al, 2020 ). At the same time, Tlr2 and Tlr4 disrupted the SGN degeneration signaling network ( Figure 3C ).…”

SK-Channel Activation Alters Peripheral Metabolic Pathways in Mice, but Not Lipopolysaccharide-Induced Fever or Inflammation

“…Interscapular BAT was dissected after skin disinfection (70% ethanol; Stockmeiern) and explant cultures had been performed as recently described with small modifications to account for the high energy needs of this highly metabolic tissue. 61 In brief, for each independent experiment, BAT from eight mice was washed with cold PBS (Capricorn Scientific), cut into ~40 mg pieces to ensure nutrient supply, and stored on ice in oxygenated Earle’s balanced salt solution (Thermo Fisher Scientific) supplemented with penicillin–streptomycin (100 U/mL, Thermo Fisher Scientific), and 20 mM HEPES (Sigma-Aldrich). For each experiment, eight wells of BAT were cultured in 12-well plates with DMEM supplemented with high glucose (GlutaMax Supplement, Thermo Fisher Scientific) containing 10% FBS (Capricorn), penicillin–streptomycin (100 U/mL), and 40 mM HEPES for 2 hours at 37°C (95% humidity, 5% CO 2 , and 95% air).…”

“…BAT-explant cultures have been used to investigate cytokine release into supernatants. 61 After collection of the supernatants, BAT was frozen on dry ice and stored at −80°C for further analyses of UCP1 expression.…”