title: Eicosapentaenoic acid inhibits tumour necrosis factor-α-induced lipolysis in murine cultured adipocytes.
abstract: Eicosapentaenoic acid (EPA) is an omega-3 polyunsaturated fatty acid with beneficial effects in obesity and insulin resistance. High levels of proinflammatory cytokine tumour necrosis factor-α (TNF-α) in obesity promote lipolysis in adipocytes, leading to the development of insulin resistance. Thus, the aims of the present study were to analyze the potential antilipolytic properties of EPA on cytokine-induced lipolysis and to investigate the possible mechanisms involved. The EPA effects on basal and TNF-α-induced lipolysis were determined in both primary rat and 3T3-L1 adipocytes. Treatment of primary rat adipocytes with EPA (100 and 200 μM) significantly decreased basal glycerol release (P<.01) and prevented cytokine-induced lipolysis in a dose-dependent manner (P<.001). Moreover, EPA decreased TNF-α-induced activation of nuclear factor-κB and extracellular-related kinase 1/2 phosphorylation. In addition, the antilipolytic action of EPA was stimulated by the AMP-kinase (AMPK) activator 5-aminoimidazole-4-carboxamide-1-b-d-ribofuranoside and blocked by the AMPK-inhibitor compound C. Moreover, we found that EPA stimulated hormone-sensitive lipase (HSL) phosphorylation on serine-565, which further supports the involvement of AMPK in EPA's antilipolytic actions. Eicosapentaenoic acid treatment (24 h), alone and in the presence of TNF-α, also decreased adipose triglyceride lipase (ATGL) protein content in cultured adipocytes. However, oral supplementation with EPA for 35 days was able to partially reverse the down-regulation of HSL and ATGL messenger RNA observed in retroperitoneal adipose tissue of high-fat-diet-fed rats. These findings suggest that EPA inhibits proinflammatory cytokine-induced lipolysis in adipocytes. This effect might contribute to explain the insulin-sensitizing properties of EPA.
authors.affiliation: Department of Nutrition, Food Science, Physiology and Toxicology, University of Navarra, 31008 Pamplona, Spain.
authors.forename: Silvia
authors.initials: S
authors.lastname: Lorente-Cebrián
authors.forename: Matilde
authors.initials: M
authors.lastname: Bustos
authors.forename: Amelia
authors.initials: A
authors.lastname: Marti
authors.forename: Marta
authors.initials: M
authors.lastname: Fernández-Galilea
authors.forename: J Alfredo
authors.initials: JA
authors.lastname: Martinez
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Moreno-Aliaga
mesh_terms: D041721:3T3-L1 Cells; D000263:Adenylate Kinase / Q000378:metabolism; D017667:Adipocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D000284:Administration, Oral; D000818:Animals; D059305:Diet, High-Fat; D015536:Down-Regulation; D015118:Eicosapentaenoic Acid / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism; D050152:Intra-Abdominal Fat / Q000378:metabolism; D008049:Lipase / Q000378:metabolism; D008066:Lipolysis; D008297:Male; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D010766:Phosphorylation; D051381:Rats; D017208:Rats, Wistar; D002787:Sterol Esterase / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism*; D000217:Acyltransferases
chemical_list: D000263:Adenylate Kinase; D015118:Eicosapentaenoic Acid; D007328:Insulin; D008049:Lipase; D016328:NF-kappa B; D002787:Sterol Esterase; D014409:Tumor Necrosis Factor-alpha; C494445:PNPLA2 protein, mouse; D000217:Acyltransferases