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 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.