Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, UK.
Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, UK; Oxford NIHR Biomedical Research Centre, Churchill Hospital, Oxford, UK.
Atherosclerosis. 2024 Jul;394:117237. doi: 10.1016/j.atherosclerosis.2023.117237. Epub 2023 Aug 11.
The prevalence of metabolic diseases, including type 2 diabetes mellitus (T2DM) and metabolic dysfunction-associated steatotic liver disease (MASLD) is increasing. Although invariably associated with obesity, the importance of fat deposition in non-adipose tissue organs has yet to be fully explored. Pathological ectopic fat deposition within the liver (known as (MASLD)) has been suggested to underlie the development of T2DM and is now emerging as an independent risk factor for cardiovascular disease (CVD). The process of hepatic de novo lipogenesis (DNL), that is the synthesis of fatty acids from non-lipid precursors (e.g. glucose), has received much attention as it sits at the intersect of hepatic glucose and fatty acid handling. An upregulation of the DNL pathway has been suggested to be central in the development of metabolic diseases (including MASLD, insulin resistance, and T2DM). Here we review the evidence to determine if hepatic DNL may play a role in the development of MASLD and T2DM and therefore underlie an increased risk of CVD.
代谢性疾病（包括 2 型糖尿病和代谢相关脂肪性肝病）的患病率正在上升。尽管肥胖是这些疾病的共同病因，但脂肪在非脂肪组织器官中的沉积的重要性尚未被充分研究。肝脏内的病理性异位脂肪沉积（即代谢相关脂肪性肝病）被认为是 2 型糖尿病发生的基础，并且现在已成为心血管疾病的独立危险因素。从头肝内脂肪生成（DNL）过程，即从非脂类前体（如葡萄糖）合成脂肪酸，由于其处于肝脏葡萄糖和脂肪酸处理的交汇点，因此受到了广泛关注。DNL 途径的上调被认为是代谢性疾病（包括代谢相关脂肪性肝病、胰岛素抵抗和 2 型糖尿病）发展的核心。在这里，我们回顾了相关证据，以确定 DNL 是否可能在代谢相关脂肪性肝病和 2 型糖尿病的发展中发挥作用，从而导致心血管疾病风险增加。
