Lipopolysaccharide induces catecholamine production in mesenteric adipose tissue of rats previously exposed to immobilization stress

Abstract

Catecholamines (CAs) are mainly produced by sympathoadrenal system but their de novo production has been also observed in adipose tissue cells. The aim of this work was to investigate whether immune challenge induced by lipopolysaccharide (LPS) modulates biosynthesis of CAs in mesenteric adipose tissue (MWAT), as well as whether previous exposure to immobilization (IMO) stress could modulate this process. Sprague-Dawley rats were exposed to single (2 h) or repeated (2 h/7 days) IMO and afterwards injected with LPS (i.p., 100 μg/kg body weight) and sacrificed 3 h later. LPS did not alter CA biosynthesis in MWAT in control rats. Single and repeated IMO elevated CAs and expression of CA biosynthetic enzymes in MWAT, including adipocyte and stromal/vascular fractions (SVF). Repeated IMO followed by LPS treatment led to the up-regulation of CA-biosynthetic enzymes expression, elevation of CAs in SVF but depletion of norepinephrine and epinephrine in adipocyte fraction. Prior IMO caused a marked LPS-induced macrophage infiltration in MWAT as evaluated by F4/80 expression. A positive correlation between expression of tyrosine hydroxylase and F4/80 suggests macrophages as the main source of LPS-induced CA production in MWAT. Furthermore, prior exposure to the single or repeated IMO differently affected immune responses following LPS treatment by modulation of inflammatory cytokine expression. These data suggest that stress might be a significant modulator of immune response in MWAT via stimulation of the macrophage infiltration associated with cytokine response and de novo production of CAs.

Continuous cold exposure induces an anti-inflammatory response in mesenteric adipose tissue associated with catecholamine production and thermogenin expression in rats

“…Recent studies have suggested that the M1-M2 switch in adipose tissues is caused by diff erential recruitment of various monocyte subtypes (Lumeng et al 2008). Since we have previously found correlation between F4/80 and TH expression in the mWAT, rising number of M2 macrophages may participate in CA production (Vargovic et al 2016). Elevated monocyte infi ltration in WAT is observed especially in obesity but with dominant M1 phenotype associated with infl ammation, resistin expression, and pathological consequences related to insulin resistance.…”

“…We have identifi ed CA biosynthetic enzymes expression in the brown and white adipose tissues and described the stimulation of CA production in the cell fractions of the mesenteric adipose tissue in response to immobilization or cold stress (Vargovic et al 2011;Kvetnansky et al 2012;Vargovic et al 2013;Vargovic et al 2016). Since only the mWAT showed stress-inducible cell-specifi c CA production, from all the investigated adipose tissues (brown, epididymal, retroperitoneal, subcutaneous), we suppose that the mWAT may represent another active site of the beige adipogenesis, similarly as it has been described in the case of the scWAT.…”

Adipocytes and macrophages secretomes coregulate catecholamine-synthesizing enzymes

“…The upregulation of TH in adipocytes and preadipocytes by IFNγ and IL-4 stimulation may reflect an increase of CA synthesis to counteract the inflammatory environment. Notably, IL-4 was also reported to increase TH expression in macrophages [10]. There was no observable difference in the expression pattern of TH, PNMT and PPARγ in preadipocytes and adipocytes after pro (INF-γ) or anti-inflammatory (IL-4) cytokines exposure.…”

“…The interplay between adipokines and CA [9] suggests a role for these molecules linking obesity to inflammation. Indeed, in rat visceral AT lipopolysaccharides (LPS) and immobilization insults modulate the immune response and increase macrophage infiltration associated with endogenous CA production [10]. CA signaling in macrophages has been reported to modulate inflammation by decreasing TNF-α secretion [14].…”

“…Immune cells, neurons and adipocytes seem to share signaling pathways mediated by catecholamines (CA) through the activation of adrenoceptors (AR) [9,10] and dopaminergic receptors present in these cells [11][12][13]. Moreover, endogenous CA through autocrine/paracrine mechanisms modulate inflammatory responses in monocytes and other immune cell types [10,14].…”