Department of Molecular Medicine, "Sapienza" University of Rome, 00161 Rome, Italy.
Department of Experimental Medicine, Section of Medical Physiopathology, Food Science and Endocrinology, "Sapienza" University of Rome, Viale del Policlinico 155, 00161 Rome, Italy.
Int J Mol Sci. 2022 Dec 13;23(24):15860. doi: 10.3390/ijms232415860.
Overnutrition and its sequelae have become a global concern due to the increasing incidence of obesity and insulin resistance. A ketogenic diet (KD) is widely used as a dietary treatment for metabolic disorders. Sirtuin1 (SIRT1), a metabolic sensor which regulates fat homeostasis, is modulated by dietary interventions. However, the influence of nutritional ketosis on SIRT1 is still debated. We examined the effect of KD on adipose tissue, liver, and serum levels of SIRT1 in mice. Adult C57BL/6J male mice were randomly assigned to two isocaloric dietary groups and fed with either high-fat KD or normal chow (NC) for 4 weeks. Serum SIRT1, beta-hydroxybutyrate (βHB), glucose, and triglyceride levels, as well as SIRT1 expression in visceral (VAT), subcutaneous (SAT), and brown (BAT) adipose tissues, and in the liver, were measured. KD-fed mice showed an increase in serum βHB in parallel with serum SIRT1 (r = 0.732, = 0.0156), and increased SIRT1 protein expression in SAT and VAT. SIRT1 levels remained unchanged in BAT and in the liver, which developed steatosis. Normal glycemia and triglycerides were observed. Under a KD, serum and white fat phenotypes show higher SIRT1, suggesting that one of the molecular mechanisms underlying a KD's potential benefits on metabolic health involves a synergistic interaction with SIRT1.
营养过剩及其后果已成为全球关注的焦点，因为肥胖症和胰岛素抵抗的发病率不断上升。生酮饮食（KD）作为一种代谢紊乱的饮食治疗方法被广泛应用。Sirtuin1（SIRT1）作为一种调节脂肪动态平衡的代谢感受器，受到饮食干预的调节。然而，营养性酮症对 SIRT1 的影响仍存在争议。我们研究了 KD 对小鼠脂肪组织、肝脏和血清 SIRT1 水平的影响。成年 C57BL/6J 雄性小鼠被随机分配到两个等热量饮食组，分别用高脂肪 KD 或正常饲料（NC）喂养 4 周。测量血清 SIRT1、β-羟丁酸（βHB）、葡萄糖和甘油三酯水平，以及内脏（VAT）、皮下（SAT）和棕色（BAT）脂肪组织以及肝脏中的 SIRT1 表达。KD 喂养的小鼠血清βHB 与血清 SIRT1 平行增加（r = 0.732， = 0.0156），SAT 和 VAT 中的 SIRT1 蛋白表达增加。BAT 和肝脏中的 SIRT1 水平保持不变，这些部位发生了脂肪变性。观察到正常的血糖和甘油三酯水平。在 KD 下，血清和白色脂肪表型显示出更高的 SIRT1，这表明 KD 对代谢健康的潜在益处的一个分子机制涉及与 SIRT1 的协同相互作用。
