title: Alternate-day fasting protects the livers of mice against high-fat diet-induced inflammation associated with the suppression of Toll-like receptor 4/nuclear factor κB signaling.
abstract: Because of unhealthy lifestyles, a large number of people are suffering from hepatic lipid accumulation and nonalcoholic steatohepatitis. Energy restriction (ER) is an effective nutritional intervention for preventing chronic disease. However, poor compliance with continuous ER limits its effectiveness. As an alternative to daily ER, alternate-day fasting (ADF) may be more effective. We hypothesized that ADF would improve obesity, hyperglycemia, and insulin resistance and protect the liver against high-fat diet (HFD)-induced steatosis and inflammation. In this study, we used C57BL/6 mice to test the beneficial effects of ADF. Thirty male 6-week-old C57BL/6 mice were divided into 3 groups (10 per group, total N = 30): 1 group was fed chow diet, the second was fed HFD ad libitum, and the third group was submitted to ADF. The mice in the third group were fed the HFD ad libitum every other day and fasted the following day. After 12 months, the mice submitted to ADF exhibited reduced body weights and fasting glucose levels and improved insulin resistance and hepatic steatosis compared with continuous HFD-fed mice. In addition, the serum transaminase levels in the mice of the ADF group were lower than those of the HFD group. Moreover, the ADF regimen suppressed the expression levels of Toll-like receptor 4 and nuclear factor κB protein in the liver and suppressed the inflammatory pathway genes interleukin 1β, tumor necrosis factor α, and serum amyloid A. These finding indicate that long-term ADF protects mouse livers against HFD-induced hepatic steatosis and hepatocellular damage associated with the suppression of Toll-like receptor 4/nuclear factor κB signaling.
authors.affiliation: Clinical laboratory, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, Jiangsu, PR China.
authors.forename: Wanwei
authors.initials: W
authors.lastname: Yang
authors.affiliation: Research Center of Endocrine and Metabolic Diseases, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, Jiangsu, PR China.
authors.forename: Meng
authors.initials: M
authors.lastname: Cao
authors.affiliation: Research Center of Endocrine and Metabolic Diseases, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, Jiangsu, PR China.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Mao
authors.affiliation: Research Center of Endocrine and Metabolic Diseases, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, Jiangsu, PR China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Wei
authors.affiliation: Research Center of Endocrine and Metabolic Diseases, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, Jiangsu, PR China.
authors.forename: Xingjia
authors.initials: X
authors.lastname: Li
authors.affiliation: Research Center of Endocrine and Metabolic Diseases, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, Jiangsu, PR China.
authors.forename: Guofang
authors.initials: G
authors.lastname: Chen
authors.affiliation: Clinical laboratory, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, Jiangsu, PR China.
authors.forename: Jiaming
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Clinical laboratory, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, Jiangsu, PR China.
authors.forename: Zhiguo
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Clinical laboratory, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, Jiangsu, PR China.
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Shi
authors.affiliation: Research Center of Endocrine and Metabolic Diseases, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, Jiangsu, PR China.
authors.forename: HouCai
authors.initials: H
authors.lastname: Huang
authors.affiliation: Clinical laboratory, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, Jiangsu, PR China. Electronic address: yaoxm73@sina.com.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Yao
authors.affiliation: Research Center of Endocrine and Metabolic Diseases, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, Jiangsu, PR China. Electronic address: profliuchao@163.com.
authors.forename: Chao
authors.initials: C
authors.lastname: Liu
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight; D059305:Diet, High-Fat / Q000009:adverse effects*; D004038:Diet, Reducing; D004195:Disease Models, Animal; D005215:Fasting; D007249:Inflammation / Q000209:etiology / Q000235:genetics / Q000517:prevention & control*; D007333:Insulin Resistance; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D065626:Non-alcoholic Fatty Liver Disease / Q000178:diet therapy / Q000517:prevention & control; D000685:Serum Amyloid A Protein / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism*; D000637:Transaminases / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D053583:Interleukin-1beta; D016328:NF-kappa B; D000685:Serum Amyloid A Protein; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D000637:Transaminases
keywords: Alternate-day fasting; Calorie restriction; Inflammation; Liver; Mouse