Major findings include: 1) metabolic stress inhibits Lcn10 expression in macrophages; 2) Lcn10 deficiency skews macrophages towards a pro-inflammatory phenotype, exacerbates insulin resistance, and impairs cardiac contractile function during diabetes conditions; 3) the Nr4a1 signaling pathway is disrupted in Lcn10-KO macrophages, leading to augmented inflammation; and 4) treatment with Nr4a1 agonist, CsnB, alleviates pro-inflammatory response in macrophages and partially improves cardiac function when comparing Lcn10-KO mice to WT controls. This evidence concerns the gene LCN10 and Insulin resistance.