title: Effects of methotrexate on inflammatory alterations induced by obesity: an in vivo and in vitro study.
abstract: Immunosuppressant drugs, such as methotrexate, are able to inhibit cytokine production and leukocyte migration to inflammatory foci; therefore, they could modify the establishment of inflammation in adipose tissue during obesity. Thus, we studied the effects of methotrexate in vivo on high-fat diet induced-obesity in mice and in vitro in isolated and co-cultured adipocytes and macrophages. Obese mice treated with methotrexate presented reduced serum levels of TNF-α, insulin and glucose, and an improvement of insulin sensitivity. Adipose tissue from these mice produced less proinflammatory (TNF-α, IL-6, leptin) and more anti-inflammatory adipokines (adiponectin and IL-10) associated with reduced macrophage infiltration and inflammation. Cytokine inhibition was also confirmed in isolated and co-cultured adipocytes and macrophages. Methotrexate presented anti-lipolytic effect in vivo and, in vitro through adenosine release. Drugs that combine anti-lipolytic effect and the ability to control inflammation in adipose tissue could play a role in the control of insulin resistance and other pathologies associated with obesity.
authors.affiliation: Clinical Pharmacology and Gastroenterology Unit, São Francisco University Medical School, Bragança Paulista, SP, Brazil.
authors.forename: Caroline Candida
authors.initials: CC
authors.lastname: DeOliveira
authors.forename: Simone Coghetto
authors.initials: SC
authors.lastname: Acedo
authors.forename: Erica Martins Ferreira
authors.initials: EM
authors.lastname: Gotardo
authors.forename: Patricia de Oliveira
authors.initials: Pde O
authors.lastname: Carvalho
authors.forename: Thalita
authors.initials: T
authors.lastname: Rocha
authors.forename: José
authors.initials: J
authors.lastname: Pedrazzoli
authors.forename: Alessandra
authors.initials: A
authors.lastname: Gambero
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D000273:Adipose Tissue / Q000187:drug effects / Q000473:pathology; D050154:Adiposity / Q000187:drug effects; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D018920:Coculture Techniques; D016207:Cytokines / Q000097:blood / Q000378:metabolism; D059305:Diet, High-Fat; D004822:Epididymis / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007249:Inflammation / Q000150:complications* / Q000378:metabolism / Q000473:pathology*; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008066:Lipolysis / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D008727:Methotrexate / Q000494:pharmacology*; D051379:Mice; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D009765:Obesity / Q000150:complications* / Q000378:metabolism / Q000473:pathology*; D010766:Phosphorylation / Q000187:drug effects
chemical_list: D016207:Cytokines; D052247:Nitric Oxide Synthase Type II; D048031:JNK Mitogen-Activated Protein Kinases; D008727:Methotrexate