Effect of acetylsalicylic acid on inflamed adipose tissue. Insulin resistance and hepatic steatosis in a mouse model of diet-induced obesity

• Published in: Life sciences (1973) Vol. 264; p. 118618
• Main Authors: Sardi, Claudia, Martini, Elisa, Mello, Tommaso, Camelliti, Simone, Sfondrini, Lucia, Marcucci, Fabrizio, Kallikourdis, Marinos, Sommariva, Michele, Rumio, Cristiano
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 01.01.2021; Elsevier BV
• Subjects: Acetylsalicylic acid; Adipocytes; Adipose tissue; Adipose Tissue - drug effects; Adipose Tissue - metabolism; Adipose Tissue - pathology; Animals; Anti-inflammatory agents; Anti-Inflammatory Agents, Non-Steroidal - pharmacology; Anti-Inflammatory Agents, Non-Steroidal - therapeutic use; Aspirin - pharmacology; Aspirin - therapeutic use; Biochemical analysis; Body weight; Body weight loss; Cardiovascular diseases; Complications; Cytokines; Diabetes mellitus; Diet; Diet, High-Fat - adverse effects; Disease Models, Animal; Fatty liver; Female; Gene expression; Global health; Hepatic steatosis; High fat diet; Hypertrophy; Inflammation; Inflammation - drug therapy; Inflammation - metabolism; Inflammation - pathology; Insulin; Insulin resistance; Insulin Resistance - physiology; Liver; Liver cancer; Lymphocytes; Macrophages; Mice; Mice, Inbred C57BL; Mouse model; Obesity; Obesity - drug therapy; Obesity - metabolism; Obesity - pathology; Public health; Risk analysis; Risk factors; Steatosis; Treatment Outcome; Weight control; Weight loss; RT; NAFLD; KO; H&E; HFD; HCC; Inflammation; DIO; WAT; Acetylsalicylic acid; Hepatic steatosis; NASH; COX; ASA; Std Dev; SD; NSAIDs; High-fat diet; Mouse model; FA; OGTT
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/j.lfs.2020.118618

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. 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. 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. ASA can efficiently ameliorate pathological conditions usually associated with obesity by inhibiting the inflammatory process occurring in the adipose tissue. •Acetylsalicylic acid can counteract the inflammatory process induced by high-fat diet consumption•Acetylsalicylic acid acts on adipose tissue reducing the release of inflammatory cytokines•Acetylsalicylic acid can revert high insulin and glucose levels induced by high-fat diet•Acetylsalicylic acid improves hepatic steatosis by a mechanism not involving the resolution of inflammation in liver