Effects and mechanisms of caffeine to improve immunological and metabolic abnormalities in diet-induced obese rats

• Published in: American journal of physiology: endocrinology and metabolism 2018-05, Vol.314 (5), p.E433-E447
• Main Authors: Liu, Chih-Wei, Tsai, Hung-Cheng, Huang, Chia-Chang, Tsai, Chang-Youh, Su, Yen-Bo, Lin, Ming-Wei, Lee, Kuei-Chuan, Hsieh, Yun-Cheng, Li, Tzu-Hao, Huang, Shiang-Fen, Yang, Ying-Ying, Hou, Ming-Chih, Lin, Han-Chieh, Lee, Fa-Yauh, Lee, Shou-Dong
• Format: Article
• Language: English
• Subjects: Abnormalities; Acetyl-CoA carboxylase; Adipose tissue; Adiposity - drug effects; Animals; Bioaccumulation; Body fat; Body weight; Caffeine; Caffeine - pharmacology; Cell adhesion; Cells, Cultured; Diet; Diet, High-Fat; Fatty acids; Fatty liver; Fatty Liver - metabolism; Fatty Liver - prevention & control; Fatty-acid synthase; Fuel consumption; High fat diet; Immune system; Immune System Diseases - etiology; Immune System Diseases - pathology; Immune System Diseases - prevention & control; Immunology; Inflammation; Inflammation - prevention & control; Insulin; Insulin Resistance; Intercellular adhesion molecule 1; Interleukin 6; Leukocyte migration; Lipogenesis; Lipogenesis - drug effects; Liver; Macrophages; Macrophages - drug effects; Macrophages - immunology; Macrophages - metabolism; Male; Metabolism; Molecular chains; Molecular modelling; Monocyte chemoattractant protein 1; Monocytes; Muscles; Obesity; Obesity - etiology; Obesity - immunology; Obesity - metabolism; Peripheral blood; Rats; Rats, Sprague-Dawley; Rodents; Sensitizing; Signal Transduction - drug effects; Steatosis; Tumor necrosis factor-α; Weight reduction
• ISSN: 0193-1849; 1522-1555
• DOI: 10.1152/ajpendo.00094.2017

In obesity, there are no effective therapies for parallel immune and metabolic abnormalities, including systemic/tissue insulin-resistance/inflammation, adiposity and hepatic steatosis. Caffeine has anti-inflammation, antihepatic steatosis, and anti-insulin resistance effects. In this study, we evaluated the effects and molecular mechanisms of 6 wk of caffeine treatment (HFD-caf) on immunological and metabolic abnormalities of high-fat diet (HFD)-induced obese rats. Compared with HFD vehicle (HFD-V) rats, in HFD-caf rats the suppressed circulating immune cell inflammatory [TNFα, MCP-1, IL-6, intercellular adhesion molecule 1 (ICAM-1), and nitrite] profiles were accompanied by decreased liver, white adipose tissue (WAT), and muscle macrophages and their intracellular cytokine levels. Metabolically, the increase in metabolic rates reduced lipid accumulation in various tissues, resulting in reduced adiposity, lower fat mass, decreased body weight, amelioration of hepatic steatosis, and improved systemic/muscle insulin resistance. Further mechanistic approaches revealed an upregulation of tissue lipogenic [(SREBP1c, fatty acid synthase, acetyl-CoA carboxylase)/insulin-sensitizing (GLUT4 and p-IRS1)] markers in HFD-caf rats. Significantly, ex vivo experiments revealed that the cytokine release by the cocultured peripheral blood mononuclear cell (monocyte) and WAT (adipocyte), which are known to stimulate macrophage migration and hepatocyte lipogenesis, were lower in HFD-V groups than HFD-caf groups. Caffeine treatment simultaneously ameliorates immune and metabolic pathogenic signals present in tissue to normalize immunolgical and metabolic abnormalities found in HFD-induced obese rats.