Obesity-mediated metabolic syndrome remains the leading cause of death worldwide. Among many potential targets for pharmacological intervention, a promising strategy involves the heme oxygenase (HO) system, specifically its inducible form, HO-1. This review collects and updates much of the current knowledge relevant to pharmacology and clinical medicine concerning HO-1 in metabolic diseases and its effect on lipid metabolism. HO-1 has pleotropic effects that collectively reduce inflammation, while increasing vasodilation and insulin and leptin sensitivity. Recent reports indicate that HO-1 with its antioxidants via the effect of bilirubin increases formation of biologically active lipid metabolites such as epoxyeicosatrienoic acid (EET), omega-3 and other polyunsaturated fatty acids (PUFAs). Similarly, HO-1and bilirubin are potential therapeutic targets in the treatment of fat-induced liver diseases. HO-1-mediated upregulation of EET is capable not only of reversing endothelial dysfunction and hypertension, but also of reversing cardiac remodeling, a hallmark of the metabolic syndrome. This process involves browning of white fat tissue (i.e. formation of healthy adipocytes) and reduced lipotoxicity, which otherwise will be toxic to the heart. More importantly, this review examines the activity of EET in biological systems and a series of pathways that explain its mechanism of action and discusses how these might be exploited for potential therapeutic use. We also discuss the link between cardiac ectopic fat deposition and cardiac function in humans, which is similar to that described in obese mice and is regulated by HO-1-EET-PGC1α signaling, a potent negative regulator of the inflammatory adipokine NOV.

肥胖介导的代谢综合征仍然是全世界死亡的主要原因。在药物干预的许多潜在目标中，一种有前途的策略涉及血红素加氧酶 (HO) 系统，特别是其诱导型 HO-1。本综述收集并更新了与代谢疾病中的 HO-1 及其对脂质代谢的影响有关的药理学和临床医学的许多当前知识。HO-1 具有多效性，可共同减少炎症，同时增加血管舒张和胰岛素和瘦素敏感性。最近的报告表明，HO-1 及其抗氧化剂通过胆红素的作用增加了具有生物活性的脂质代谢物的形成，例如环氧二十碳三烯酸 (EET)、omega-3 和其他多不饱和脂肪酸 (PUFA)。相似地，HO-1和胆红素是治疗脂肪性肝病的潜在治疗靶点。HO-1 介导的 EET 上调不仅能够逆转内皮功能障碍和高血压，而且能够逆转心脏重塑，这是代谢综合征的标志。这个过程涉及白色脂肪组织的褐变（即健康脂肪细胞的形成）和降低的脂毒性，否则将对心脏产生毒性。更重要的是，本综述检查了 EET 在生物系统中的活性以及解释其作用机制的一系列途径，并讨论了如何将这些途径用于潜在的治疗用途。我们还讨论了心脏异位脂肪沉积与人类心脏功能之间的联系，这与肥胖小鼠中描述的相似，受 HO-1-EET-PGC1α 信号传导的调节，