Pentraxin 3 deficiency exacerbates lipopolysaccharide-induced inflammation in adipose tissue

Abstract

Background/objectives Pentraxin 3 (PTX3) has been characterized as a soluble and multifunctional pattern recognition protein in the regulation of innate immune response. However, little is known about its role in adipose tissue inflammation and obesity. Herein, we investigated the role of PTX3 in the regulation of lipopolysaccharide (LPS)-induced inflammation in adipocytes and adipose tissue, as well as high-fat diet (HFD)-induced metabolic inflammation in obesity. Methods Ptx3 knockdown 3T3-L1 Cells were generated using shRNA for Ptx3 gene and treated with different inflammatory stimuli. For the in vivo studies, Ptx3 knockout mice were treated with 0.3 mg/kg of LPS for 6 h. Adipose tissues were collected for gene and protein expression by qPCR and western blotting, respectively. Ptx3 knockout mice were fed with HFD for 12 week since 6 week of age. Results We observed that the expression of PTX3 in adipose tissue and serum PTX3 were markedly increased in response to LPS administration. Knocking down Ptx3 in 3T3-L1 cells reduced adipogenesis and caused a more profound and sustained upregulation of proinflammatory gene expression and signaling pathway activation during LPS-stimulated inflammation in 3T3-L1 adipocytes. In vivo studies showed that PTX3 deficiency significantly exacerbated the LPS-induced upregulation of inflammatory genes and downregulation of adipogeneic genes in visceral and subcutaneous adipose tissue of mice. Accordingly, LPS stimulation elicited increased activation of nuclear factor-κB (NF-κB) and p44/42 MAPK (Erk1/2) signaling pathways in visceral and subcutaneous adipose tissue. The expression of PTX3 in adipose tissue was also induced by HFD, and PTX3 deficiency led to the upregulation of proinflammatory genes in visceral adipose tissue of HFD-induced obese mice. Conclusions Our results suggest a protective role of PTX3 in LPS-and HFD-induced sustained inflammation in adipose tissue.

Vesicles Shed by Pathological Murine Adipocytes Spread Pathology: Characterization and Functional Role of Insulin Resistant/Hypertrophied Adiposomes

“…Thus, we detected that pentraxin-3 protein is seven times elevated in MSCs vesicles compared to those from the same cells after differentiation. This protein has a protective role in LPS and high fat diet-induced inflammation in murine adipose tissue [55], thus, it may suggest a functional anti-inflammatory role of those vesicles secreted by MSCs as previously described [56].…”

Pentraxin 3 Regulates miR‐21 Expression and Secretion in Brown Adipocytes During Lipopolysaccharide‐Induced Inflammation

“…Although eWAT expressed the highest levels of PTX3 among three fat depots, the expression levels of miR‐21 and miR‐146 were very low and not regulated by PTX3 deficiency in eWAT in male mice. Interestingly, our previous studies in female mice showed that BAT and iWAT expressed higher levels of PTX3 than eWAT . Taken together, our results suggest that PTX3, which displays a sex and depot difference in its expression, regulates inflammation possibly through a different mechanism in different adipose depots as well as between the sexes.…”

“…However, the role of PTX3 in adipocyte inflammation and how PTX3 regulates the inflammatory process in adipocytes are not fully understood. Our previous study showed that knocking down PTX3 exacerbated lipopolysaccharide (LPS)–induced inflammation in adipocytes, and the peak of LPS‐induced PTX3 expression in adipose tissue appeared later than that of the expression of inflammatory cytokines and the activation of nuclear factor (NF)‐κB. These results suggest that PTX3 functions in resolving inflammation.…”

Proficiency of Extracellular Vesicles From hiPSC-Derived Neural Stem Cells in Modulating Proinflammatory Human Microglia: Role of Pentraxin-3 and miRNA-21-5p

“…PTX3 also plays a role in synaptogenesis in the developing brain ( Fossati et al, 2019 ). Furthermore, PTX3 deficiency results in augmented infarct area following myocardial ischemia/reperfusion injury ( Salio et al, 2008 ), increased macrophage accumulation and inflammation in atherosclerotic plaques ( Norata et al, 2009 ), and exacerbated proinflammatory gene expression in visceral adipose tissue from a high fat diet-induced obese mice ( Guo et al, 2020 ). Overall, PTX3 can mediate multiple beneficial effects in various disease states through antiinflammatory and neuroprotective actions.…”