Oxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital, Oxford, UK.
Oxford NIHR Biomedical Research Centre, Churchill Hospital, Oxford, UK.
Diabetes Obes Metab. 2019 Apr;21(4):749-760. doi: 10.1111/dom.13592. Epub 2018 Dec 21.
Non-alcoholic fatty liver disease (NAFLD) encompasses a spectrum of liver diseases, of which the first stage is steatosis. It is one of the most common liver diseases in developed countries and there is a clear association between type 2 diabetes (T2DM) and NAFLD. It is estimated that 70% of people with T2DM have NAFLD and yet there is currently no licensed pharmacological agent to treat it. Whilst lifestyle modification may ameliorate liver fat, it is often difficult to achieve or sustain; thus, there is great interest in pharmacological treatments for NAFLD. Metformin is the first-line medication in the management of T2DM and evidence from animal and human studies has suggested that it may be useful in reducing liver fat via inhibition of lipogenesis and increased fatty acid oxidation. Findings from the majority of studies undertaken in rodent models clearly suggest that metformin may be a powerful therapeutic agent specifically to reduce liver fat accumulation; data from human studies are less convincing. In the present review we discuss the evidence for the specific effects of metformin treatment on liver fat accumulation in animal and human studies, as well as the underlying proposed mechanisms, to try and understand and reconcile the difference in findings between rodent and human work in this area.
非酒精性脂肪性肝病（NAFLD）涵盖了一系列肝脏疾病，其中第一阶段是脂肪变性。它是发达国家最常见的肝脏疾病之一，2 型糖尿病（T2DM）与 NAFLD 之间有明确的关联。据估计，70%的 T2DM 患者患有 NAFLD，但目前尚无治疗该病的批准药物。虽然生活方式的改变可能会改善肝脏脂肪，但往往难以实现或维持；因此，人们对治疗 NAFLD 的药物治疗非常感兴趣。二甲双胍是 T2DM 治疗的一线药物，动物和人体研究的证据表明，它可能通过抑制脂肪生成和增加脂肪酸氧化来减少肝脏脂肪。在啮齿动物模型中进行的大多数研究的结果清楚地表明，二甲双胍可能是一种特别有效的治疗药物，专门用于减少肝脏脂肪堆积；来自人体研究的数据则不太令人信服。在本综述中，我们讨论了二甲双胍治疗对动物和人体研究中肝脏脂肪堆积的具体作用的证据，以及潜在的拟议机制，试图理解和调和这一领域中啮齿动物和人体工作结果之间的差异。
