title: The apelinergic system: sexual dimorphism and tissue-specific modulations by obesity and insulin resistance in female mice.
abstract: It has been proposed that the apelinergic system (apelin and its receptor APJ) may be a promising therapeutic target in obesity-associated insulin resistance syndrome. However, due to the extended tissue-distribution of this system, the therapeutic use of specific ligands for APJ may target numerous tissues resulting putatively to collateral deleterious effects. To unravel specific tissular dysfunctions of this system under obesity and insulin-resistance conditions, we measured the apelinemia and gene-expression level of both apelin (APL) and APJ in 12-selected tissues of insulin-resistant obese female mice fed with a high fat (HF) diet. In a preliminary study, we compared between adult male and female mice, the circadian plasma apelin variation and the effect of fasting on apelinemia. No significant differences were found for these parameters suggesting that the apelinemia is not affected by the sex. Moreover, plasma apelin level was not modulated during the four days of the estrous cycle in females. In obese and insulin-resistant HF female mice, plasma apelin concentration after fasting was not modified but, the gene-expression level of the APL/APJ system was augmented in the white adipose tissue (WAT) and reduced in the brown adipose tissue (BAT), the liver and in kidneys. BAT apelin content was reduced in HF female mice. Our data suggest that the apelinergic system may be implicated into specific dysfunctions of these tissues under obesity and diabetes and that, pharmacologic modulations of this system may be of interest particularly in the treatment of adipose, liver and renal dysfunctions that occur during these pathologies.
authors.affiliation: Unité Environnement Périnatal et Croissance, EA 4489, Faculté de Médecine, Université Lille Nord de France, Pôle Recherche, IFR 114, 59045 Lille, France.
authors.forename: Laura
authors.initials: L
authors.lastname: Butruille
authors.forename: Anne
authors.initials: A
authors.lastname: Drougard
authors.forename: Claude
authors.initials: C
authors.lastname: Knauf
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Moitrot
authors.forename: Philippe
authors.initials: P
authors.lastname: Valet
authors.forename: Laurent
authors.initials: L
authors.lastname: Storme
authors.forename: Philippe
authors.initials: P
authors.lastname: Deruelle
authors.forename: Jean
authors.initials: J
authors.lastname: Lesage
mesh_terms: D054392:Adipokines; D002001:Adipose Tissue, Brown / Q000378:metabolism; D052436:Adipose Tissue, White / Q000378:metabolism; D000818:Animals; D000073861:Apelin; D000075244:Apelin Receptors; D002940:Circadian Rhythm; D059305:Diet, High-Fat; D030762:Estrous Cycle / Q000097:blood; D005215:Fasting / Q000097:blood; D005260:Female; D007333:Insulin Resistance / Q000502:physiology*; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood* / Q000235:genetics*; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000097:blood / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D043562:Receptors, G-Protein-Coupled / Q000235:genetics*; D012737:Sex Factors
chemical_list: D054392:Adipokines; D000073861:Apelin; D000075244:Apelin Receptors; C402826:Apln protein, mouse; C491285:Aplnr protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled
keywords: Apelin/APJ; Diabetes; Mouse; Obesity; Sexual dimorphism