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长期间歇性禁食与代谢相关脂肪性肝病

石丹^1,2, 练雪梅^1,2, 阮雄中^1,*

¹重庆医科大学感染性疾病分子生物学教育部重点实验室、脂质研究中心，重庆 400016；²重庆医科大学公共卫生学院营养与食品卫生学教研室，重庆 400016

摘要

近几年来，间歇性禁食(intermittent fasting, IF)由于其显著改善机体健康代谢作用受到广泛的关注。IF是指间断性地极少或者不摄入含有热量的食物的饮食模式[1, 2]。IF包括三种饮食形式： 隔日禁食(alternate day fasting, ADF)、限时饮食(time-restricted feeding, TRF)以及每周中有2天禁食的5:2饮食[1, 2]。其中ADF是指每隔1天禁食或者极少量进食24 h，但不限制饮水及其他无热量食物的摄入[1, 2]。先前大量的动物以及人群研究证实了ADF的有益作用，包括减轻体重、增强胰岛素敏感性、改善代谢综合征风险指标，抑制肿瘤发生与发展以及延缓衰老，并且这种有益作用无论在长期还是短期研究中都得到了有效证实[1–5]。9周的ADF显著降低高脂肪饮食诱导的C57BL/6J 雄性小鼠体重和脂肪含量增加，并且与限时饮食以及能量限制饮食相比，ADF显示出最佳的空腹血糖水平和葡萄糖耐量 [6]。Meta分析进一步发现1~2个月的ADF与健康成人，以及超重、肥胖或非酒精性脂肪肝成人的体质指数降低相关[7]。另一项随机临床试验探讨了长期的ADF对代谢健康的肥胖成年人体重的影响，结果发现6个月的ADF显著降低机体体重以及血清瘦素的水平[8, 9]。虽然有少量研究也探讨了ADF对非肥胖健康人群的影响，并发现了其对体重与空腹胰岛素的降低作用[10]，然而绝大多数研究主要关注非健康人群或者高脂肪饮食下的动物疾病模型，在正常饮食背景下长期的间歇性禁食是否仍然对健康个体具有有益的改善作用，需要更多的研究进一步证实。在本期《生理学报》杂志上，龚鹏飞等人以 C57BL/6N雌性成年小鼠为模型，采用4个月ADF方式探讨长期间歇性禁食对小鼠健康及肝脏脂质代谢的影响[11]。研究分为两组：自由进食组(Ad Libitum)和ADF组。研究结果发现，与自由进食组相比，ADF组小鼠的体重显著降低，糖脂代谢水平改善，这与先前一系列的研究报道一致[3, 5, 7, 9, 12]。然而ADF同时引起小鼠肝脏脂质积累增加，具体表现为肝脏指数以及肝脏甘油三酯含量显著增加，同时伴随着肝脏脂代谢基因以及自噬活性增强。

Prolonged intermittent fasting and metabolic-related fatty liver disease

SHI Dan^1,2, LIAN Xue-Mei^1,2, RUAN Xiong-Zhong^1,*

¹Key Laboratory of Molecular Biology of infectious diseases of Ministry of Education, Center of Lipid Research, Chongqing Medical University, Chongqing 400016, China；²Department of Nutrition and Food Hygiene, College of Public Health, Chongqing Medical University, Chongqing 400016, China

Abstract

In recent years, intermittent fasting (IF) has attracted extensive attention due to its significant improvement of body health metabolism. IF refers to the diet pattern of intermittent little or no intake of food containing calories [1,2]. IF includes three types of diet: alternate day fasting (ADF), time limited feeding (TRF), and 5:2 diet with two days of fasting every week [1,2]. Among them, ADF refers to fasting every other day or taking a very small amount of food for 24 hours, but does not limit the intake of drinking water and other calorie free foods [1,2]. A large number of previous animal and human studies have confirmed the beneficial effects of ADF, including weight loss, insulin sensitivity enhancement, improvement of risk indicators of metabolic syndrome, inhibition of tumor occurrence and development, and anti-aging, and this beneficial effect has been effectively confirmed in both long-term and short-term studies [1 – 5]. The 9-week ADF significantly reduced the weight and fat content of C57BL/6J male mice induced by high-fat diet, and showed the best fasting blood glucose level and glucose tolerance compared with the time limited diet and energy limited diet [6]. Meta analysis further found that ADF of 1-2 months was associated with the decrease of body mass index in healthy adults and overweight, obese or nonalcoholic fatty liver adults [7]. Another randomized clinical trial explored the effect of long-term ADF on the weight of obese adults with metabolic health, and found that 6-month ADF significantly reduced body weight and serum leptin levels [8, 9]. Although a small number of studies have also explored the impact of ADF on non-obese healthy people, and found its role in reducing body weight and fasting insulin [10], most studies focus on non-healthy people or animal disease models under high-fat diet. Whether long-term intermittent fasting under the background of normal diet still has a beneficial improvement effect on healthy individuals needs further confirmation by more studies. In this issue of Acta Physiologica Sinica, Gong et al. used C57BL/6N female adult mice as models to explore the effects of long-term intermittent fasting on the health of mice and liver lipid metabolism in the way of 4-month ADF [11]. The study was divided into two groups: Ad Libitum group and ADF group. The results showed that compared with the free eating group, the ADF group mice had significantly lower body weight and improved glucose and lipid metabolism, which was consistent with a series of previous studies [3, 5, 7, 9, 12]. However, ADF also caused an increase in liver lipid accumulation in mice, specifically, liver index and liver triglyceride content increased significantly, accompanied by an increase in liver lipid metabolism genes and autophagic activity.

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通讯作者：阮雄中　　E-mail: xiongzruan@foxmail.com

引用本文：

石丹, 练雪梅, 阮雄中. 长期间歇性禁食与代谢相关脂肪性肝病[J]. 生理学报 2022; 74 (6): 959-961.

SHI Dan, LIAN Xue-Mei, RUAN Xiong-Zhong. Prolonged intermittent fasting and metabolic-related fatty liver disease. Acta Physiol Sin 2022; 74 (6): 959-961 (in Chinese with English abstract).