Claudia Sardi1, Elisa Martini2, Tommaso Mello3, Simone Camelliti4, Lucia Sfondrini4, Fabrizio Marcucci5, Marinos Kallikourdis6, Michele Sommariva4, Cristiano Rumio7. 1. Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, via Trentacoste 2, Milan, Italy; Adaptive Immunity Laboratory, Humanitas Clinical and Research Center IRCCS, Via Manzoni 56, 20089 Rozzano, Italy. 2. Adaptive Immunity Laboratory, Humanitas Clinical and Research Center IRCCS, Via Manzoni 56, 20089 Rozzano, Italy. 3. Scienze Biomediche, Sperimentali e Cliniche 'Mario Serio', Università degli Studi di Firenze, Viale Pieraccini 6, 50139 Florence, Italy. 4. Dipartimento di Scienze Biomediche per la Salute, Università degli Studi di Milano, Via Mangiagalli 31, 20133 Milan, Italy. 5. Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, via Trentacoste 2, Milan, Italy. 6. Adaptive Immunity Laboratory, Humanitas Clinical and Research Center IRCCS, Via Manzoni 56, 20089 Rozzano, Italy; Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20090 Pieve Emanuele, Italy. 7. Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, via Trentacoste 2, Milan, Italy. Electronic address: cristiano.rumio@unimi.it.
Abstract
AIMS: Obesity represents a global health problem. Excessive caloric intake promotes the release of inflammatory mediators by hypertrophic adipocytes and obesity-induced inflammation is now recognized as a risk factor for the development of several diseases, such as cardiovascular diseases, insulin resistance, type-II diabetes, liver steatosis and cancer. Since obesity causes inflammation, we tested the ability of acetylsalicylic acid (ASA), a potent anti-inflammatory drug, in counteracting this inflammatory process and in mitigating obesity-associated health complications. MAIN METHODS: Mice were fed with standard (SD) or high fat diet (HFD) for 3 months and then treated with acetylsalicylic acid for the subsequent two months. We then analyzed the metabolic and inflammatory status of their adipose and liver tissue by histological, molecular and biochemical analysis. KEY FINDINGS: Although ASA did not exert any effect on body weight, quantification of adipocyte size revealed that the drug slightly reduced adipocyte hypertrophy, however not sufficient so as to induce weight loss. Most importantly, ASA was able to improve insulin resistance. Gene expression profiles of pro- and anti-inflammatory cytokines as well as the expression of macrophage and lymphocyte markers revealed that HFD led to a marked macrophage accumulation in the adipose tissue and an increase of several pro-inflammatory cytokines, a situation almost completely reverted after ASA administration. In addition, liver steatosis caused by HFD was completely abrogated by ASA treatment. SIGNIFICANCE: ASA can efficiently ameliorate pathological conditions usually associated with obesity by inhibiting the inflammatory process occurring in the adipose tissue.
AIMS: Obesity represents a global health problem. Excessive caloric intake promotes the release of inflammatory mediators by hypertrophic adipocytes and obesity-induced inflammation is now recognized as a risk factor for the development of several diseases, such as cardiovascular diseases, insulin resistance, type-II diabetes, liver steatosis and cancer. Since obesity causes inflammation, we tested the ability of acetylsalicylic acid (ASA), a potent anti-inflammatory drug, in counteracting this inflammatory process and in mitigating obesity-associated health complications. MAIN METHODS:Mice were fed with standard (SD) or high fat diet (HFD) for 3 months and then treated with acetylsalicylic acid for the subsequent two months. We then analyzed the metabolic and inflammatory status of their adipose and liver tissue by histological, molecular and biochemical analysis. KEY FINDINGS: Although ASA did not exert any effect on body weight, quantification of adipocyte size revealed that the drug slightly reduced adipocyte hypertrophy, however not sufficient so as to induce weight loss. Most importantly, ASA was able to improve insulin resistance. Gene expression profiles of pro- and anti-inflammatory cytokines as well as the expression of macrophage and lymphocyte markers revealed that HFD led to a marked macrophage accumulation in the adipose tissue and an increase of several pro-inflammatory cytokines, a situation almost completely reverted after ASA administration. In addition, liver steatosis caused by HFD was completely abrogated by ASA treatment. SIGNIFICANCE: ASA can efficiently ameliorate pathological conditions usually associated with obesity by inhibiting the inflammatory process occurring in the adipose tissue.