Molecular Medicine University of Western Ontario, London, Ontario, Canada N6A 5B7; Robarts Research Institute, Departments of Biochemistry University of Western Ontario, London, Ontario, Canada N6A 5B7.
Molecular Medicine University of Western Ontario, London, Ontario, Canada N6A 5B7.
J Lipid Res. 2018 Sep;59(9):1714-1728. doi: 10.1194/jlr.M087387. Epub 2018 Jul 15.
Obesity and its associated metabolic dysfunction and cardiovascular disease risk represent a leading cause of adult morbidity worldwide. Currently available pharmacological therapies for obesity have had limited success in reversing existing obesity and metabolic dysregulation. Previous prevention studies demonstrated that the citrus flavonoids, naringenin and nobiletin, protect against obesity and metabolic dysfunction in mice fed a high-fat cholesterol-containing (HFHC) diet. However, their effects in an intervention model are unknown. In this report, we show that, in mice with diet-induced obesity, citrus flavonoid supplementation to a HFHC diet reversed existing obesity and adipocyte size and number through enhanced energy expenditure and increased hepatic fatty acid oxidation. Caloric intake was unaffected and no evidence of white adipose tissue browning was observed. Reversal of adiposity was accompanied by improvements in hyperlipidemia, insulin sensitivity, hepatic steatosis, and a modest reduction in blood monocytes. Together, this resulted in atherosclerotic lesions that were unchanged in size, but characterized by reduced macrophage content, consistent with a more stable plaque phenotype. These studies further suggest potential therapeutic utility of citrus flavonoids, especially in the context of existing obesity, metabolic dysfunction, and cardiovascular disease.
肥胖及其相关的代谢功能障碍和心血管疾病风险是全球成年人发病的主要原因。目前用于肥胖的药物疗法在逆转现有肥胖和代谢失调方面收效甚微。先前的预防研究表明，柑橘类黄酮柚皮苷和川陈皮素可预防高脂肪胆固醇饮食喂养的肥胖和代谢功能障碍。然而，它们在干预模型中的作用尚不清楚。在本报告中，我们发现，在饮食诱导肥胖的肥胖症中，柑橘类黄酮补充高脂肪胆固醇饮食可通过增加能量消耗和增加肝脏脂肪酸氧化来逆转现有的肥胖症和脂肪细胞大小和数量。热量摄入不受影响，也没有观察到白色脂肪组织褐变的证据。脂肪量的减少伴随着高脂血症、胰岛素敏感性、肝脂肪变性的改善，以及血液单核细胞的适度减少。总的来说，这导致动脉粥样硬化病变的大小不变，但巨噬细胞含量减少，与更稳定的斑块表型一致。这些研究进一步表明，柑橘类黄酮具有潜在的治疗用途，特别是在现有的肥胖症、代谢功能障碍和心血管疾病的情况下。
