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

Chih Wei Liu, Hung Cheng Tsai, Chia Chang Huang, Chang Youh Tsai, Yen Bo Su, Ming Wei Lin, Kuei Chuan Lee, Yun Cheng Hsieh, Tzu Hao Li, Shiang Fen Huang, Ying Ying Yang*, Ming Chih Hou, Han Chieh Lin, Fa Yauh Lee, Shou Dong Lee

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

19 Scopus citations


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 antiinflammation, 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.

Original languageEnglish
Pages (from-to)E433-E447
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Issue number5
StatePublished - May 2018


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