Zhang Shaohong, Sun Shuoshuo, Wei Xiao, Zhang Mengxiao, Chen Yu, Mao Xiaodong, Chen Guofang, Liu Chao
Endocrinology Department, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China.
Department of Geriatrics, The Affiliated Huaian No. 1 People's Hospital, Nanjing Medical University, Nanjing, China.
Food Nutr Res. 2022 May 3;66. doi: 10.29219/fnr.v66.7909. eCollection 2022.
Obesity is a growing problem for public health worldwide. Calorie restriction (CR) is a safety and effective life intervention to defend against obesity. Short-term moderate CR may be a more favorable strategy against this pathology. However, the mechanisms behind the effects of CR remain to be clarified. Increased energy expenditure in the liver and brown adipose tissue could potentially be manipulated to modulate and improve metabolism in obesity. Moreover, nicotinamide adenine dinucleotide (NAD)-dependent deacetylase sirtuin-1 (SIRT1) and AMP-activated protein kinase (AMPK) are well-characterized metabolic modulators. We aim to explore the anti-obesity effects of short-term moderate CR by improving energy metabolism via the SIRT1/AMPK pathway in white adipocytes and liver in a mouse model of obesity.
Male C57BL/6 mice were randomized into two groups receiving either a standard or a high-fat diet (HFD) for 8 weeks to induce obesity. The HFD-induced obese mice were further randomized into two groups: HFD group or CR group (received 75% of the food eaten by HFD group). Their energy metabolism, white adipose tissue (WAT) contents, hepatic fat deposition, the expression of AMPK, SIRT1, peroxisome proliferators γ-activated receptor coactivator-1α (PGC-1α), nuclear factor kappa B (NF-κB), endothelial nitric oxide synthase (eNOS) in WAT, and hepatic tissues were determined.
After 4 weeks, body weight, total serum cholesterol, fasting blood glucose, and insulin levels were significantly lower in the CR group. Moreover, CR ameliorated hepatocyte steatosis, attenuated white adipogenesis, and increased energy expenditure and expressions of SIRT1, PGC-1α, and phosphorylated AMPK in subcutaneous WAT and the hepatic tissues. In addition, CR reduced the protein levels of NF-κB and increased the eNOS expression.
Short-term moderate CR decreases obesity, increases the thermogenesis, and inhibits inflammation in a mouse model of obesity, probably via the activation of the AMPK/SIRT1 pathway in WAT and liver.
肥胖是全球公共卫生领域日益严重的问题。热量限制（CR）是一种安全有效的预防肥胖的生活干预措施。短期适度的热量限制可能是对抗这种病理状况的更有利策略。然而，热量限制作用背后的机制仍有待阐明。肝脏和棕色脂肪组织中能量消耗的增加可能会被调控，以调节和改善肥胖状态下的新陈代谢。此外，烟酰胺腺嘌呤二核苷酸（NAD）依赖性去乙酰化酶沉默调节蛋白1（SIRT1）和AMP活化蛋白激酶（AMPK）是已被充分表征的代谢调节因子。我们旨在通过在肥胖小鼠模型中经由白色脂肪细胞和肝脏中的SIRT1/AMPK途径改善能量代谢，来探索短期适度热量限制的抗肥胖作用。
将雄性C57BL/6小鼠随机分为两组，分别给予标准饮食或高脂饮食（HFD）8周以诱导肥胖。将高脂饮食诱导的肥胖小鼠进一步随机分为两组：高脂饮食组或热量限制组（摄入高脂饮食组所进食食物的75%）。测定它们的能量代谢、白色脂肪组织（WAT）含量、肝脏脂肪沉积、WAT和肝脏组织中AMPK、SIRT1、过氧化物酶体增殖物激活受体γ共激活因子-1α（PGC-1α）、核因子κB（NF-κB）、内皮型一氧化氮合酶（eNOS）的表达。
4周后，热量限制组的体重、总血清胆固醇、空腹血糖和胰岛素水平显著降低。此外，热量限制改善了肝细胞脂肪变性，减轻了白色脂肪生成，并增加了皮下WAT和肝脏组织中的能量消耗以及SIRT1、PGC-1α和磷酸化AMPK的表达。此外，热量限制降低了NF-κB的蛋白水平并增加了eNOS的表达。
短期适度的热量限制可减轻肥胖小鼠模型的体重，增加产热并抑制炎症，可能是通过激活WAT和肝脏中的AMPK/SIRT1途径实现的。
