
收稿日期: 2024-09-30
录用日期: 2025-03-13
网络出版日期: 2025-07-14
基金资助
上海市浦江人才计划(22PJD034);上海交通大学青年人才培育计划(2022QN028)
Research progress in effects and mechanisms of dietary pattern interventions in metabolic associated fatty liver disease
Received date: 2024-09-30
Accepted date: 2025-03-13
Online published: 2025-07-14
Supported by
Shanghai Pujiang Program(22PJD034);Youth Talent Training Program of Shanghai Jiao Tong University(2022QN028)
代谢相关脂肪性肝病(metabolic associated fatty liver disease,MAFLD)是一种与全身代谢紊乱相关的脂肪性肝病,其患病率逐年攀升,已成为全球公共卫生的重大挑战。MAFLD的发生与肥胖、血脂异常、糖尿病等多种因素相关:体内过多脂肪堆积,尤其是内脏脂肪增加,会使肝脏脂肪积聚;血脂异常也会扰乱肝脏脂肪代谢;糖尿病患者因胰岛素抵抗等问题,患MAFLD风险大增。饮食干预被认为是预防和治疗MAFLD的有效手段。近年来,低碳水化合物饮食、间歇性禁食和地中海饮食等膳食模式已被应用于临床实践。其主要作用机制包括减少氧化应激、调控肠道菌群以及诱导脂肪自噬等。然而,不同个体基因、生活方式及疾病程度的差异导致其对不同饮食模式的反应各异。因此,系统评估这些饮食模式在MAFLD防治中的效果及机制具有重要的临床意义。该文通过比较不同膳食模式在改善肝功能、肝脏脂肪含量、血糖及血脂等方面的效果,分析其潜在干预机制,探讨如何根据个体差异选择个性化饮食策略,为MAFLD的精准防治提供新思路,助力改善患者预后,减轻公共卫生负担。
宋静 , 姜烁 , 万方煜 , 李娟 , 艾迪娜·木合塔 , 闵新颖 , 周婧琪 . 膳食模式干预对代谢相关脂肪性肝病的影响与机制研究进展[J]. 上海交通大学学报(医学版), 2025 , 45(7) : 926 -933 . DOI: 10.3969/j.issn.1674-8115.2025.07.015
Metabolic associated fatty liver disease (MAFLD) is a type of fatty liver disease associated with systemic metabolic disorders, and its prevalence has been increasing year by year, becoming a major challenge to global public health. The development of MAFLD is associated with various factors, including obesity, dyslipidemia, diabetes and other factors. Excessive body fat, particularly increased visceral adiposity, contributes to hepatic fat accumulation. Abnormal blood lipid levels can also disrupt liver fat metabolism. The risk of MAFLD in patients with diabetes is greatly increased due to insulin resistance and other problems. Dietary interventions are considered an effective strategy for the prevention and treatment of MAFLD. In recent years, several dietary patterns, such as low-carbohydrate diets, intermittent fasting, and the Mediterranean diet, have been applied in clinical practice. Their primary mechanisms include reducing oxidative stress, regulating gut microbiota, and inducing fat autophagy. However, the responses to different dietary patterns vary among individuals due to differences in genes, lifestyle, and disease severity. Therefore, systematically evaluating the effects and mechanisms of these dietary patterns in the prevention and treatment of MAFLD has significant clinical importance. This review compares the effects of different dietary patterns on improving liver function, hepatic fat content, blood glucose, and lipid levels, and analyzes their underlying mechanisms of intervention, to explore how to select personalized dietary strategies based on individual differences. It is intended to provide new insights for the precise prevention and treatment of MAFLD, thereby improving patients′ outcomes and alleviating the burden on public health.
| [1] | ESLAM M, FAN J G, YU M L, et al. The Asian Pacific Association for the Study of the Liver clinical practice guidelines for the diagnosis and management of metabolic dysfunction-associated fatty liver disease[J]. Hepatol Int, 2025, 19(2): 261-301. |
| [2] | ESLAM M, SARIN S K, WONG V W, et al. The Asian Pacific Association for the Study of the Liver clinical practice guidelines for the diagnosis and management of metabolic associated fatty liver disease[J]. Hepatol Int, 2020, 14(6): 889-919. |
| [3] | 范建高, 杨荣. 全球非酒精性脂肪性肝病的流行趋势与疾病负担[J]. 中华消化杂志, 2023, 43(4): 248-252. |
| FAN J G, YANG R. Global prevalence trends and disease burden of non-alcoholic fatty liver disease[J]. Chinese Journal of Digestion, 2023, 43(4): 248-252. | |
| [4] | RONG L, ZOU J Y, RAN W, et al. Advancements in the treatment of non-alcoholic fatty liver disease (NAFLD)[J]. Front Endocrinol (Lausanne), 2023, 13: 1087260. |
| [5] | MASCARó C M, BOUZAS C, TUR J A. Association between non-alcoholic fatty liver disease and Mediterranean lifestyle: a systematic review[J]. Nutrients, 2021, 14(1): 49. |
| [6] | WEI S L, WANG L, EVANS P C, et al. NAFLD and NASH: etiology, targets and emerging therapies[J]. Drug Discov Today, 2024, 29(3): 103910. |
| [7] | YOO E R, KIM D, VAZQUEZ-MONTESINO L M, et al. Diet quality and its association with nonalcoholic fatty liver disease and all-cause and cause-specific mortality[J]. Liver Int, 2020, 40(4): 815-824. |
| [8] | CLAYTON-CHUBB D, KEMP W, MAJEED A, et al. Understanding NAFLD: from case identification to interventions, outcomes, and future perspectives[J]. Nutrients, 2023, 15(3): 687. |
| [9] | SIMANCAS-RACINES D, ANNUNZIATA G, VERDE L, et al. Nutritional strategies for battling obesity-linked liver disease: the role of medical nutritional therapy in metabolic dysfunction-associated steatotic liver disease (MASLD) management[J]. Curr Obes Rep, 2025, 14(1): 7. |
| [10] | ASGHARI S, REZAEI M, RAFRAF M, et al. Effects of calorie restricted diet on oxidative/antioxidative status biomarkers and serum fibroblast growth factor 21 levels in nonalcoholic fatty liver disease patients: a randomized, controlled clinical trial[J]. Nutrients, 2022, 14(12): 2509. |
| [11] | BALDRY E L, AITHAL G P, KAYE P, et al. Effects of short-term energy restriction on liver lipid content and inflammatory status in severely obese adults: results of a randomized controlled trial using 2 dietary approaches[J]. Diabetes Obes Metab, 2017, 19(8): 1179-1183. |
| [12] | MONSERRAT-MESQUIDA M, QUETGLAS-LLABRéS M, ABBATE M, et al. Oxidative stress and pro-inflammatory status in patients with non-alcoholic fatty liver disease[J]. Antioxidants (Basel), 2020, 9(8): 759. |
| [13] | GóMEZ-SáMANO M á, GRAJALES-GóMEZ M, ZUARTH-VáZQUEZ J M, et al. Fibroblast growth factor 21 and its novel association with oxidative stress[J]. Redox Biol, 2017, 11: 335-341. |
| [14] | TILLMAN E J, ROLPH T. FGF21: an emerging therapeutic target for non-alcoholic steatohepatitis and related metabolic diseases[J]. Front Endocrinol (Lausanne), 2020, 11: 601290. |
| [15] | LU P, ZHANG F C, QIAN S W, et al. Artemisinin derivatives prevent obesity by inducing browning of WAT and enhancing BAT function[J]. Cell Res, 2016, 26(10): 1169-1172. |
| [16] | SARIS C G J, TIMMERS S. Ketogenic diets and ketone suplementation: a strategy for therapeutic intervention[J]. Front Nutr, 2022, 9: 947567. |
| [17] | HOLMER M, LINDQVIST C, PETERSSON S, et al. Treatment of NAFLD with intermittent calorie restriction or low-carb high-fat diet: a randomised controlled trial[J]. JHEP Rep, 2021, 3(3): 100256. |
| [18] | CHEN J, HUANG Y Q, XIE H, et al. Impact of a low-carbohydrate and high-fiber diet on nonalcoholic fatty liver disease[J]. Asia Pac J Clin Nutr, 2020, 29(3): 483-490. |
| [19] | LUUKKONEN P K, DUFOUR S, LYU K, et al. Effect of a ketogenic diet on hepatic steatosis and hepatic mitochondrial metabolism in nonalcoholic fatty liver disease[J]. Proc Natl Acad Sci USA, 2020, 117(13): 7347-7354. |
| [20] | CUNHA G M, GUZMAN G, CORREA DE MELLO L L, et al. Efficacy of a 2-month very low-calorie ketogenic diet (VLCKD) compared to a standard low-calorie diet in reducing visceral and liver fat accumulation in patients with obesity[J]. Front Endocrinol (Lausanne), 2020, 11: 607. |
| [21] | MINISTRINI S, CALZINI L, NULLI MIGLIOLA E, et al. Lysosomal acid lipase as a molecular target of the very low carbohydrate ketogenic diet in morbidly obese patients: the potential effects on liver steatosis and cardiovascular risk factors[J]. J Clin Med, 2019, 8(5): 621. |
| [22] | DAHL W J, RIVERO MENDOZA D, LAMBERT J M. Diet, nutrients and the microbiome[J]. Prog Mol Biol Transl Sci, 2020, 171: 237-263. |
| [23] | MARDINOGLU A, WU H, BJORNSON E, et al. An integrated understanding of the rapid metabolic benefits of a carbohydrate-restricted diet on hepatic steatosis in humans[J]. Cell Metab, 2018, 27(3): 559-571.e5. |
| [24] | CRABTREE C D, KACKLEY M L, BUGA A, et al. Comparison of ketogenic diets with and without ketone salts versus a low-fat diet: liver fat responses in overweight adults[J]. Nutrients, 2021, 13(3): 966. |
| [25] | 叶俊钊, 林衍松, 钟碧慧. 代谢相关脂肪性肝病饮食干预新策略的研究进展[J]. 临床肝胆病杂志, 2021, 37(3): 709-713. |
| YE J Z, LIN Y S, ZHONG B H. Research advances in dietary intervention in the treatment of metabolic associated fatty liver disease[J]. Journal of Clinical Hepatology, 2021, 37(3): 709-713. | |
| [26] | 徐大凤, 王凯丁. 高蛋白膳食对超重/肥胖成人肾功能、体重、血脂影响[J]. 包头医学院学报, 2021, 37(9): 5-10. |
| XU D F, WANG K D. Effects of high protein diet on renal function, weight, and lipids in overweight/obese adults[J]. Journal of Baotou Medical College, 2021, 37(9): 5-10. | |
| [27] | SUN P, HUANG L P, SHUAI P, et al. Effect of a high protein, low glycemic index dietary intervention on metabolic dysfunction-associated fatty liver disease: a randomized controlled trial[J]. Front Nutr, 2022, 9: 863834. |
| [28] | XU C C, MARKOVA M, SEEBECK N, et al. High-protein diet more effectively reduces hepatic fat than low-protein diet despite lower autophagy and FGF21 levels[J]. Liver Int, 2020, 40(12): 2982-2997. |
| [29] | MARKOVA M, PIVOVAROVA O, HORNEMANN S, et al. Isocaloric diets high in animal or plant protein reduce liver fat and inflammation in individuals with type 2 diabetes[J]. Gastroenterology, 2017, 152(3): 571-585.e8. |
| [30] | MOON J, KOH G. Clinical evidence and mechanisms of high-protein diet-induced weight loss[J]. J Obes Metab Syndr, 2020, 29(3): 166-173. |
| [31] | DE CHIARA F, URETA CHECCLLO C, RAMóN AZCóN J. High protein diet and metabolic plasticity in non-alcoholic fatty liver disease: myths and truths[J]. Nutrients, 2019, 11(12): 2985. |
| [32] | LUDWIG D S, HU F B, LICHTENSTEIN A H, et al. Low-fat diet redux at WHO[J]. Am J Clin Nutr, 2023, 118(5): 849-851. |
| [33] | 雷雷, 赵妍娟, 高风双, 等. 低碳水化合物饮食与低脂饮食干预对老年非酒精性脂肪肝患者糖脂代谢水平及肝功能影响[J]. 社区医学杂志, 2022, 20(18): 1051-1056. |
| LEI L, ZHAO Y J, GAO F S, et al. Effects of low-carbohydrate diet and low-fat diet on glucose-lipid metabolism indexes and liver function in elderly patients with non-alcoholic fatty liver disease[J]. Journal of Community Medicine, 2022, 20(18): 1051-1056. | |
| [34] | RISTIC-MEDIC D, KOVACIC M, TAKIC M, et al. Calorie-restricted Mediterranean and low-fat diets affect fatty acid status in individuals with nonalcoholic fatty liver disease[J]. Nutrients, 2020, 13(1): 15. |
| [35] | XIONG Y L, SHI X Y, XIONG X Y, et al. A systematic review and meta-analysis of randomized controlled trials: effects of Mediterranean diet and low-fat diet on liver enzymes and liver fat content of NAFLD[J]. Food Funct, 2024, 15(16): 8248-8257. |
| [36] | HENKE C, HAUFE S, ZIEHL D, et al. Low-fat hypocaloric diet reduces neprilysin in overweight and obese human subjects[J]. ESC Heart Fail, 2021, 8(2): 938-942. |
| [37] | ERDEM N B, KAHRAMANO?LU AKSOY E, DIKMEN D, et al. Effects of low fat diet on inflammatory parameters in individuals with obesity/overweight and non-alcoholic fatty liver disease: a cross-sectional study[J]. Medicine (Baltimore), 2024, 103(15): e37716. |
| [38] | SONG X L, KESTIN M, SCHWARZ Y, et al. A low-fat high-carbohydrate diet reduces plasma total adiponectin concentrations compared to a moderate-fat diet with no impact on biomarkers of systemic inflammation in a randomized controlled feeding study[J]. Eur J Nutr, 2016, 55(1): 237-246. |
| [39] | Ró?A?SKI G, PHEBY D, NEWTON J L, et al. Effect of different types of intermittent fasting on biochemical and anthropometric parameters among patients with metabolic-associated fatty liver disease (MAFLD): a systematic review[J]. Nutrients, 2021, 14(1): 91. |
| [40] | CAI H, QIN Y L, SHI Z Y, et al. Effects of alternate-day fasting on body weight and dyslipidaemia in patients with non-alcoholic fatty liver disease: a randomised controlled trial[J]. BMC Gastroenterol, 2019, 19(1): 219. |
| [41] | FEEHAN J, MACK A, TUCK C, et al. Time-restricted fasting improves liver steatosis in non-alcoholic fatty liver disease: a single blinded crossover trial[J]. Nutrients, 2023, 15(23): 4870. |
| [42] | LINDQVIST C, HOLMER M, HAGSTR?M H, et al. Macronutrient composition and its effect on body composition changes during weight loss therapy in patients with non-alcoholic fatty liver disease: secondary analysis of a randomized controlled trial[J]. Nutrition, 2023, 110: 111982. |
| [43] | YIN C, LI Z H, XIANG Y L, et al. Effect of intermittent fasting on non-alcoholic fatty liver disease: systematic review and meta-analysis[J]. Front Nutr, 2021, 8: 709683. |
| [44] | BADRAN H, ELSABAAWY M, SAKR A, et al. Impact of intermittent fasting on laboratory, radiological, and anthropometric parameters in NAFLD patients[J]. Clin Exp Hepatol, 2022, 8(2): 118-124. |
| [45] | PATIKORN C, ROUBAL K, VEETTIL S K, et al. Intermittent fasting and obesity-related health outcomes: an umbrella review of meta-analyses of randomized clinical trials[J]. JAMA Netw Open, 2021, 4(12): e2139558. |
| [46] | CHO Y, HONG N, KIM K W, et al. The effectiveness of intermittent fasting to reduce body mass index and glucose metabolism: a systematic review and meta-analysis[J]. J Clin Med, 2019, 8(10): 1645. |
| [47] | MINCIUNA I, GALLAGE S, HEIKENWALDER M, et al. Intermittent fasting: the future treatment in NASH patients?[J]. Hepatology, 2023, 78(4): 1290-1305. |
| [48] | MARJOT T, TOMLINSON J W, HODSON L, et al. Timing of energy intake and the therapeutic potential of intermittent fasting and time-restricted eating in NAFLD[J]. Gut, 2023, 72(8): 1607-1619. |
| [49] | LAVALLEE C M, BRUNO A, MA C, et al. The role of intermittent fasting in the management of nonalcoholic fatty liver disease: a narrative review[J]. Nutrients, 2022, 14(21): 4655. |
| [50] | LI D Z, DUN Y S, QI D K, et al. Intermittent fasting activates macrophage migration inhibitory factor and alleviates high-fat diet-induced nonalcoholic fatty liver disease[J]. Sci Rep, 2023, 13: 13068. |
| [51] | DEL BO′ C, PERNA S, ALLEHDAN S, et al. Does the Mediterranean diet have any effect on lipid profile, central obesity and liver enzymes in non-alcoholic fatty liver disease (NAFLD) subjects? A systematic review and meta-analysis of randomized control trials[J]. Nutrients, 2023, 15(10): 2250. |
| [52] | BIOLATO M, MANCA F, MARRONE G, et al. Intestinal permeability after Mediterranean diet and low-fat diet in non-alcoholic fatty liver disease[J]. World J Gastroenterol, 2019, 25(4): 509-520. |
| [53] | KALIORA A C, GIOXARI A, KALAFATI I P, et al. The effectiveness of Mediterranean diet in nonalcoholic fatty liver disease clinical course: an intervention study[J]. J Med Food, 2019, 22(7): 729-740. |
| [54] | HAIGH L, KIRK C, EL GENDY K, et al. The effectiveness and acceptability of Mediterranean diet and calorie restriction in non-alcoholic fatty liver disease (NAFLD): a systematic review and meta-analysis[J]. Clin Nutr, 2022, 41(9): 1913-1931. |
| [55] | LEE J Y, KIM S, LEE Y, et al. Higher adherence to the Mediterranean diet is associated with a lower risk of steatotic, alcohol-related, and metabolic dysfunction-associated steatotic liver disease: a retrospective analysis[J]. Nutrients, 2024, 16(20): 3551. |
| [56] | MUSSO G, CASSADER M, PASCHETTA E, et al. Bioactive lipid species and metabolic pathways in progression and resolution of nonalcoholic steatohepatitis[J]. Gastroenterology, 2018, 155(2): 282-302.e8. |
| [57] | BARBER T M, KABISCH S, PFEIFFER A F H, et al. The effects of the Mediterranean diet on health and gut microbiota[J]. Nutrients, 2023, 15(9): 2150. |
/
| 〈 |
|
〉 |