Short-term moderate caloric restriction in a high-fat diet alleviates obesity via AMPK/SIRT1 signaling in white adipocytes and liver

  • Shaohong Zhang Endocrinology Department, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing; and Department of Geriatrics, The Affiliated Huaian No. 1 People’s Hospital, Nanjing Medical University, Nanjing, China
  • Shuoshuo Sun Endocrinology Department, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China
  • Xiao Wei Endocrinology Department, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China
  • Mengxiao Zhang Endocrinology Department, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing; and Department of Geriatrics, Yancheng TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Yancheng, China
  • Yu Chen Endocrinology Department, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China
  • Xiaodong Mao Endocrinology Department, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China
  • Guofang Chen Endocrinology Department, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China
  • Chao Liu Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine
Keywords: Obesity, Calorie restriction, High-fat diet, AMPK/SIRT1 pathway

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

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Published
2022-05-03
How to Cite
ZhangS., SunS., WeiX., ZhangM., ChenY., MaoX., Chen G., & LiuC. (2022). Short-term moderate caloric restriction in a high-fat diet alleviates obesity via AMPK/SIRT1 signaling in white adipocytes and liver. Food & Nutrition Research, 66. https://doi.org/10.29219/fnr.v66.7909
Section
Original Articles