Radiology Center, Bach Mai hospital, Hanoi, Vietnam.
Division of Endocrinology and Metabolism, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taiwan; Division of Endocrinology and Metabolism, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan.
J Nutr Biochem. 2023 Jan;111:109161. doi: 10.1016/j.jnutbio.2022.109161. Epub 2022 Sep 29.
The ketogenic diet (KD) might improve cardiac function in diabetic cardiomyopathy, but the mechanisms remain unclear. This study investigated the effects of KD on myocardial fatty acid (FA), glucose, and ketone metabolism in diabetic cardiomyopathy. Echocardiograms, biochemistry, and micro-positron emission tomography were performed to evaluate cardiac function and glucose uptake in control rats and streptozotocin-induced diabetes mellitus (DM) rats with normal diet (ND) or KD for 6 weeks. Histopathology, adenosine triphosphate measurement, and Western blot were performed in the ventricular myocytes to analyze fibrosis, FA, ketone body, and glucose utilization. The ND-fed DM rats exhibited impaired left ventricular systolic function and increased chamber dilatation, whereas control and KD-fed DM rats did not. The KD reduced myocardial fibrosis and apoptosis in the DM rats. Myocardial glucose uptake in the micro-positron emission tomography was similar between ND-fed DM rats and KD-fed DM rats and was substantially lower than the control rats. Compared with the control rats, ND-fed DM rats had increased phosphorylation of acetyl CoA carboxylase and higher expressions of CD-36, carnitine palmitoyltransferase-1β, tumor necrosis factor-α, interleukin-1β, interleukin6, PERK, and e-IF2α as well as more myocardial fibrosis and apoptosis (assessed by Bcl-2, BAX, and caspase-3 expression); these increases were attenuated in the KD-fed DM rats. Moreover, ND-fed DM rats had significantly lower myocardial adenosine triphosphate, BHB, and OXCT1 levels than the control and KD-fed DM rats. The KD may improve the condition of diabetic cardiomyopathy by suppressing FA metabolism, increasing ketone utilization, and decreasing endoplasmic reticulum stress and inflammation.
生酮饮食（KD）可能改善糖尿病心肌病中的心脏功能，但机制尚不清楚。本研究探讨了 KD 对糖尿病心肌病中心肌脂肪酸（FA）、葡萄糖和酮体代谢的影响。通过超声心动图、生物化学和微正电子发射断层扫描评估对照大鼠和链脲佐菌素诱导的糖尿病（DM）大鼠在正常饮食（ND）或 KD 喂养 6 周后的心脏功能和葡萄糖摄取情况。在心室肌细胞中进行组织病理学、三磷酸腺苷测量和 Western blot 分析以分析纤维化、FA、酮体和葡萄糖利用。ND 喂养的 DM 大鼠表现出左心室收缩功能受损和心室扩张增加，而对照和 KD 喂养的 DM 大鼠则没有。KD 降低了 DM 大鼠的心肌纤维化和凋亡。微正电子发射断层扫描中的心肌葡萄糖摄取在 ND 喂养的 DM 大鼠和 KD 喂养的 DM 大鼠之间相似，且明显低于对照大鼠。与对照大鼠相比，ND 喂养的 DM 大鼠乙酰辅酶 A 羧化酶磷酸化增加，CD-36、肉毒碱棕榈酰转移酶-1β、肿瘤坏死因子-α、白细胞介素-1β、白细胞介素 6、PERK 和 eIF2α 表达升高，心肌纤维化和凋亡增加（通过 Bcl-2、BAX 和 caspase-3 表达评估）；这些在 KD 喂养的 DM 大鼠中减弱。此外，ND 喂养的 DM 大鼠的心肌三磷酸腺苷、BHB 和 OXCT1 水平明显低于对照和 KD 喂养的 DM 大鼠。KD 通过抑制 FA 代谢、增加酮体利用以及减少内质网应激和炎症可能改善糖尿病心肌病的状况。
