All-trans-retinoic acid represses chemokine expression in adipocytes and adipose tissue by inhibiting NF-κB signaling.
An effect of the Vitamin A metabolite all-trans-retinoic acid (ATRA) on body weight regulation and adiposity has been described, but little is known about its impact on obesity-associated inflammation. Our objective was to evaluate the overall impact of this metabolite on inflammatory response in human and mouse adipocytes, using high-throughput methods, and to confirm its effects in a mouse model. ATRA (2 μM for 24 h) down-regulated the mRNA expression of 17 chemokines in human adipocytes, and limited macrophage migration in a TNFα-conditioned 3 T3-L1 adipocyte medium (73.7%, P<.05). These effects were confirmed in mice (n=6-9 per group) subjected to oral gavage of ATRA (5 mg/kg of body weight) and subsequently injected intraperitoneally with lipopolysaccharide. In this model, both systemic and adipose levels of inflammatory markers were reduced. The antiinflammatory effect of ATRA was associated with a reduction in the phosphorylation levels of IκB and p65 (~50%, P<.05), two subunits of the NF-κB pathway, probably mediated by PGC1α, in 3 T3-L1 adipocytes. Taken together, these results show a significant overall antiinflammatory effect of ATRA on proinflammatory cytokine and chemokine production in adipocyte and adipose tissue and suggest that ATRA supplementation may represent a strategy of preventive nutrition to fight against obesity and its complications.
NORT, Aix-Marseille Université, INRA, INSERM, 13000, Marseille, France.
Esma
E
Karkeni
NORT, Aix-Marseille Université, INRA, INSERM, 13000, Marseille, France.
Lauriane
L
Bonnet
NORT, Aix-Marseille Université, INRA, INSERM, 13000, Marseille, France.
Julien
J
Astier
NORT, Aix-Marseille Université, INRA, INSERM, 13000, Marseille, France.
Charlène
C
Couturier
NORT, Aix-Marseille Université, INRA, INSERM, 13000, Marseille, France.
Julie
J
Dalifard
NORT, Aix-Marseille Université, INRA, INSERM, 13000, Marseille, France.
Franck
F
Tourniaire
NORT, Aix-Marseille Université, INRA, INSERM, 13000, Marseille, France. Electronic address: jean-francois.landrier@univ-amu.fr.
Jean-François
JF
Landrier
D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects* / Q000378:metabolism; D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D018925:Chemokines / Q000378:metabolism*; D019587:Dietary Supplements; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism*; D015434:Panniculitis / Q000188:drug therapy; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D059467:Transcriptome / Q000187:drug effects; D014212:Tretinoin / Q000494:pharmacology*
D018925:Chemokines; D008070:Lipopolysaccharides; D016328:NF-kappa B; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C485290:Ppargc1a protein, mouse; D014212:Tretinoin
ATRA; Adipocyte; Chemokines; Inflammatory response; Macrophage migration, NF-κB