Obesity increases the risk of metabolic syndrome including insulin resistance, dyslipidemia, and cardiovascular disease. We demonstrated insulin resistance, cardiac hypertrophy, and cardiac inflammation in an obese mouse model induced by a high-fat diet (HFD). Caspase recruitment domain-containing protein 9 (CARD9) and B-cell lymphoma/leukemia 10 (BCL10) were upregulated, and p38 MAPK was activated in these mice. Zinc supplementation prevented these changes with upregulation of metallothionein (MT). Deletion of