Recombinant human relaxin-2 (serelaxin) has been widely proven as a novel drug with myriad effects at different cardiovascular levels, which support its potential therapeutic efficacy in several cardiovascular diseases (CVD). Considering these effects, together with the influence of relaxin-2 on adipocyte physiology and adipokine secretion, and the connection between visceral adipose tissue (VAT) dysfunction and the development of CVD, we could hypothesize that relaxin-2 may regulate VAT metabolism. Our objective was to evaluate the impact of a 2-week serelaxin treatment on the proteome and lipidome of VAT from Sprague-Dawley rats. We found that serelaxin increased 1 polyunsaturated fatty acid and 6 lysophosphatidylcholines and decreased 4 triglycerides in VAT employing ultra-high performance liquid chromatography-mass spectrometry (UHPLC-MS) based platforms, and that regulates 47 phosphoproteins using SWATH/MS analysis. Through RT-PCR, we found that serelaxin treatment also caused an effect on VAT lipolysis through an increase in the mRNA expression of hormonesensitive lipase (HSL) and a decrease in the expression of adipose triglyceride lipase (ATGL), together with a reduction in the VAT expression of the fatty acid transporter cluster of differentiation 36 (Cd36). Serelaxin also caused an anti-inflammatory effect in VAT by the decrease in the mRNA expression of tumor necrosis factor alpha (TNF alpha), interleukin-1 beta (IL-1 beta), chemerin, and its receptor. In conclusion, our results highlight the regulatory role of serelaxin in the VAT proteome and lipidome, lipolytic function, and inflammatory profile, suggesting the implication of several mechanisms supporting the potential benefit of serelaxin for the prevention of obesity and metabolic disorders.
Human recombinant relaxin-2 (serelaxin) regulates the proteome, lipidome, lipid metabolism and inflammatory profile of rat visceral adipose tissue / Aragón-Herrera, Alana; Feijóo-Bandín, Sandra; Vázquez-Abuín, Xocas; Anido-Varela, Laura; Moraña-Fernández, Sandra; Bravo, Susana B.; Tarazón, Estefanía; Roselló-Lletí, Esther; Portolés, Manuel; García-Seara, Javier; Seijas, José; Rodríguez-Penas, Diego; Bani, Daniele; Gualillo, Oreste; González-Juanatey, José Ramón; Lago, Francisca. - In: BIOCHEMICAL PHARMACOLOGY. - ISSN 0006-2952. - ELETTRONICO. - 223:(2024), pp. 116157.0-116157.0. [10.1016/j.bcp.2024.116157]
Human recombinant relaxin-2 (serelaxin) regulates the proteome, lipidome, lipid metabolism and inflammatory profile of rat visceral adipose tissue
Bani, DanieleMembro del Collaboration Group
;
2024
Abstract
Recombinant human relaxin-2 (serelaxin) has been widely proven as a novel drug with myriad effects at different cardiovascular levels, which support its potential therapeutic efficacy in several cardiovascular diseases (CVD). Considering these effects, together with the influence of relaxin-2 on adipocyte physiology and adipokine secretion, and the connection between visceral adipose tissue (VAT) dysfunction and the development of CVD, we could hypothesize that relaxin-2 may regulate VAT metabolism. Our objective was to evaluate the impact of a 2-week serelaxin treatment on the proteome and lipidome of VAT from Sprague-Dawley rats. We found that serelaxin increased 1 polyunsaturated fatty acid and 6 lysophosphatidylcholines and decreased 4 triglycerides in VAT employing ultra-high performance liquid chromatography-mass spectrometry (UHPLC-MS) based platforms, and that regulates 47 phosphoproteins using SWATH/MS analysis. Through RT-PCR, we found that serelaxin treatment also caused an effect on VAT lipolysis through an increase in the mRNA expression of hormonesensitive lipase (HSL) and a decrease in the expression of adipose triglyceride lipase (ATGL), together with a reduction in the VAT expression of the fatty acid transporter cluster of differentiation 36 (Cd36). Serelaxin also caused an anti-inflammatory effect in VAT by the decrease in the mRNA expression of tumor necrosis factor alpha (TNF alpha), interleukin-1 beta (IL-1 beta), chemerin, and its receptor. In conclusion, our results highlight the regulatory role of serelaxin in the VAT proteome and lipidome, lipolytic function, and inflammatory profile, suggesting the implication of several mechanisms supporting the potential benefit of serelaxin for the prevention of obesity and metabolic disorders.File | Dimensione | Formato | |
---|---|---|---|
Aragon-Herrera et al 2024.pdf
Accesso chiuso
Tipologia:
Pdf editoriale (Version of record)
Licenza:
Tutti i diritti riservati
Dimensione
5.32 MB
Formato
Adobe PDF
|
5.32 MB | Adobe PDF | Richiedi una copia |
I documenti in FLORE sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.