title: Inhibition of age-related cytokines production by ATGL: a mechanism linked to the anti-inflammatory effect of resveratrol.
abstract: Ageing is characterized by the expansion and the decreased vascularization of visceral adipose tissue (vAT), disruption of metabolic activities, and decline of the function of the immune system, leading to chronic inflammatory states. We previously demonstrated that, in vAT of mice at early state of ageing, adipocytes mount a stress resistance response consisting in the upregulation of ATGL, which is functional in restraining the production of inflammatory cytokines. Here, we found that, in the late phase of ageing, such an adaptive response is impaired. In particular, 24-months-old mice and aged 3T3-L1 adipocytes display affected expression of ATGL and its downstream PPARα-mediated lipid signalling pathway, leading to upregulation of TNFα and IL-6 production. We show that the natural polyphenol compound resveratrol (RSV) efficiently suppresses the expression of TNFα and IL-6 in an ATGL/PPARα dependent manner. Actually, adipocytes downregulating ATGL do not show a restored PPARα expression and display elevated cytokines production. Overall the results obtained highlight a crucial function of ATGL in inhibiting age-related inflammation and reinforce the idea that RSV could represent a valid natural compound to limit the onset and/or the exacerbation of the age-related inflammatory states.
authors.affiliation: Department of Biology, University of Rome Tor Vergata, Via della Ricerca Scientifica, 00133 Rome, Italy.
authors.forename: Daniele
authors.initials: D
authors.lastname: Lettieri Barbato
authors.affiliation: Scientific Institute for Research, Hospitalization and Health Care, Università Telematica San Raffaele, Via di Val Cannuta, 00167 Rome, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Tatulli
authors.affiliation: Department of Biology, University of Rome Tor Vergata, Via della Ricerca Scientifica, 00133 Rome, Italy.
authors.forename: Katia
authors.initials: K
authors.lastname: Aquilano
authors.affiliation: Department of Biology, University of Rome Tor Vergata, Via della Ricerca Scientifica, 00133 Rome, Italy ; Scientific Institute for Research, Hospitalization and Health Care, San Raffaele Pisana, Via di Val Cannuta, 00163 Rome, Italy.
authors.forename: Maria R
authors.initials: MR
authors.lastname: Ciriolo
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D016207:Cytokines / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism; D008049:Lipase / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D047493:PPAR alpha / Q000378:metabolism; D047495:PPAR gamma / Q000378:metabolism; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D000217:Acyltransferases
chemical_list: D016207:Cytokines; D015850:Interleukin-6; D008049:Lipase; D047493:PPAR alpha; D047495:PPAR gamma; D000077185:Resveratrol; D013267:Stilbenes; D014409:Tumor Necrosis Factor-alpha; C494794:PNPLA2 protein, human; D000217:Acyltransferases