慢性肝病并发肌肉脂肪变性的研究进展

孙锦涛; 栗凤霞

doi:10.3969/j.issn.1001-5256.2023.02.031

慢性肝病并发肌肉脂肪变性的研究进展

DOI: 10.3969/j.issn.1001-5256.2023.02.031

孙锦涛,
栗凤霞^, ,

山西医科大学第五临床医学院消化内科，太原 030012

基金项目:

山西省医学重点科技项目 (2020XM23)

利益冲突声明：所有作者均声明不存在利益冲突。

作者贡献声明：孙锦涛负责调研整理文献，资料分析，设计论文框架，撰写论文；栗凤霞负责指导撰写文章并最后定稿。

详细信息

通信作者:
栗凤霞，doctorlfx@163.com (ORCID：0000-0002-6712-0491)

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出版历程
- 收稿日期: 2022-07-01
- 录用日期: 2022-08-12
- 出版日期: 2023-02-20

Research advances in myosteatosis in chronic liver diseases

Jintao SUN,
Fengxia LI^{,
,}

Department of Gastroenterology, The Fifth Clinical Medical College of Shanxi Medical University, Taiyuan 030012, China

Research funding:

Shanxi Province Key Medical Science and Technology Project (2020XM23)

More Information

Corresponding author: LI Fengxia, doctorlfx@163.com (ORCID: 0000-0002-6712-0491)

摘要

摘要: 肌肉脂肪变性是营养不良的主要表现形式，是慢性肝病常见的并发症，对肝脏疾病的进展和预后具有负面影响。肌肉脂肪变性暂无诊断金标准，CT为常用的诊断方法。慢性肝病并发肌脂肪变性的机制是多样的，高氨血症、循环中组织蛋白酶D水平升高、胰岛素抵抗、线粒体功能障碍、慢性系统性微炎症等在慢性肝病肌脂肪化中起重要作用，尽早对其进行干预可改善预后。结合国内外研究现状对肌脂肪变性的特点、诊断方法、发病机制、治疗与干预方面进行了综述。
- 肝疾病 /
- 营养不良 /
- 肌肉脂肪化 /
- 病理状态, 体征和症状
Abstract: Myosteatosis is the main manifestation of malnutrition and is a common complication of chronic liver diseases, with a negative impact on the progression and prognosis of liver diseases. There is no gold standard for the diagnosis of myosteatosis, and CT is a commonly used diagnostic method. Myosteatosis in chronic liver diseases has diverse mechanisms, and hyperammonemia, increased cathepsin D level in circulation, insulin resistance, mitochondrial dysfunction, and chronic systemic microinflammation play an important role in myosteatosis. Early intervention of these factors can improve prognosis. With reference to related studies in China and globally, this article reviews the features, diagnostic methods, pathogenesis, treatment, and intervention of myosteatosis.
- Liver Diseases /
- Malnutrition /
- Myosteatosis /
- Pathological Conditions, Signs and Symptoms

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图 1 慢性肝病相关肌脂肪化机制示意图

注：CTSD，组织蛋白酶D；FFA，游离脂肪酸。

Figure 1. Schematic diagram of the mechanism of muscle steatosis associated with chronic liver disease

下载: 全尺寸图片幻灯片

参考文献(29)

[1]	EBADI M, TSIEN C, BHANJI RA, et al. Myosteatosis in cirrhosis: a review of diagnosis, pathophysiological mechanisms and potential interventions[J]. Cells, 2022, 11(7). DOI: 10.3390/cells11071216.
[2]	BHANJI RA, MOCTEZUMA-VELAZQUEZ C, DUARTE-ROJO A, et al. Myosteatosis and sarcopenia are associated with hepatic encephalopathy in patients with cirrhosis[J]. Hepatol Int, 2018, 12(4): 377-386. DOI: 10.1007/s12072-018-9875-9.
[3]	FENG H, WANG X, MAO L, et al. Relationship between sarcopenia/myosteatosis and frailty in hospitalized patients with cirrhosis: a sex-stratified analysis[J]. Ther Adv Chronic Dis, 2021, 12: 20406223211026996. DOI: 10.1177/20406223211026996.
[4]	MONTANO-LOZA AJ, ANGULO P, MEZA-JUNCO J, et al. Sarcopenic obesity and myosteatosis are associated with higher mortality in patients with cirrhosis[J]. J Cachexia Sarcopenia Muscle, 2016, 7(2): 126-135. DOI: 10.1002/jcsm.12039.
[5]	LIU YY, CHEN DF, YAN QX. Current status of the pathogenesis, diagnosis, and treatment of sarcopenia in patients with liver cirrhosis[J]. J Clin Hepatol, 2022, 38(1): 191-195. DOI: 10.3696/j.issn.1001-5256.2022.01.033. 刘钰懿, 陈东风, 颜綦先. 肝硬化肌少症的发病机制与诊疗现状[J]. 临床肝胆病杂志, 2022, 38(1): 191-195. DOI: 10.3696/j.issn.1001-5256.2022.01.033.
[6]	GUMUCIO JP, QASAWA AH, FERRARA PJ, et al. Reduced mitochondrial lipid oxidation leads to fat accumulation in myosteatosis[J]. FASEB J, 2019, 33(7): 7863-7881. DOI: 10.1096/fj.201802457RR.
[7]	KHURANA P, YADATI T, GOYAL S, et al. Inhibiting extracellular cathepsin d reduces hepatic steatosis in sprague-dawley rats[J]. Biomolecules, 2019, 9(5): 171. DOI: 10.3390/biom9050171.
[8]	KANG JK, KIM OH, HUR J, et al. Increased intracellular Ca2+ concentrations prevent membrane localization of PH domains through the formation of Ca2+-phosphoinositides[J]. Proc Natl Acad Sci U S A, 2017, 114(45): 11926-11931. DOI: 10.1073/pnas.1706489114.
[9]	DING L, DE MUNCK T, OLIGSCHLAEGER Y, et al. Myosteatosis in NAFLD patients correlates with plasma Cathepsin D[J]. Biomol Concepts, 2021, 12(1): 27-35. DOI: 10.1515/bmc-2021-0004.
[10]	DING L, HOUBEN T, OLIGSCHLAEGER Y, et al. Plasma cathepsin d activity rather than levels correlates with metabolic parameters of type 2 diabetes in male individuals[J]. Front Endocrinol (Lausanne), 2020, 11: 575070. DOI: 10.3389/fendo.2020.575070.
[11]	DONGIOVANNI P, STENDER S, PIETRELLI A, et al. Causal relationship of hepatic fat with liver damage and insulin resistance in nonalcoholic fatty liver[J]. J Intern Med, 2018, 283(4): 356-370. DOI: 10.1111/joim.12719.
[12]	PETERSEN MC, SHULMAN GI. Mechanisms of Insulin action and insulin resistance[J]. Physiol Rev, 2018, 98(4): 2133-2223. DOI: 10.1152/physrev.00063.2017.
[13]	JANA BA, CHINTAMANENI PK, KRISHNAMURTHY PT, et al. Cytosolic lipid excess-induced mitochondrial dysfunction is the cause or effect of high fat diet-induced skeletal muscle insulin resistance: a molecular insight[J]. Mol Biol Rep, 2019, 46(1): 957-963. DOI: 10.1007/s11033-018-4551-7.
[14]	MORALES PE, BUCAREY JL, ESPINOSA A. Muscle lipid metabolism: role of lipid droplets and perilipins[J]. J Diabetes Res, 2017, 2017: 1789395. DOI: 10.1155/2017/1789395.
[15]	ZHANG LR, WANG SQ, WANG HY, et al. Effect of mitochondrial dysfunction introduced by chronic liver injury in rats[J]. J China Med Univ, 2020, 49(8): 747-751. DOI: 10.12007/j.issn.0258-4646.2020.08.015. 张靓睿, 王诗琪, 王红昀, 等. 大鼠慢性肝损伤的线粒体功能障碍及其影响[J]. 中国医科大学学报, 2020, 49(8): 747-751. DOI: 10.12007/j.issn.0258-4646.2020.08.015.
[16]	LI CW, YU K, SHYH-CHANG N, et al. Pathogenesis of sarcopenia and the relationship with fat mass: descriptive review[J]. J Cachexia Sarcopenia Muscle, 2022, 13(2): 781-794. DOI: 10.1002/jcsm.12901.
[17]	MOROZZI G, BECCAFICO S, BIANCHI R, et al. Oxidative stress-induced S100B accumulation converts myoblasts into brown adipocytes via an NF-κB/YY1/miR-133 axis and NF-κB/YY1/BMP-7 axis[J]. Cell Death Differ, 2017, 24(12): 2077-2088. DOI: 10.1038/cdd.2017.132.
[18]	HAN J, MENG Q, SHEN L, et al. Interleukin-6 induces fat loss in cancer cachexia by promoting white adipose tissue lipolysis and browning[J]. Lipids Health Dis, 2018, 17(1): 14. DOI: 10.1186/s12944-018-0657-0.
[19]	MASTROCOLA R, COLLINO M, NIGRO D, et al. Accumulation of advanced glycation end-products and activation of the SCAP/SREBP Lipogenetic pathway occur in diet-induced obese mouse skeletal muscle[J]. PLoS One, 2015, 10(3): e0119587. DOI: 10.1371/journal.pone.0119587.
[20]	NACHIT M, DE RUDDER M, THISSEN JP, et al. Myosteatosis rather than sarcopenia associates with non-alcoholic steatohepatitis in non-alcoholic fatty liver disease preclinical models[J]. J Cachexia Sarcopenia Muscle, 2021, 12(1): 144-158. DOI: 10.1002/jcsm.12646.
[21]	BHANJI RA, MOCTEZUMA-VELAZQUEZ C, DUARTE-ROJO A, et al. Myosteatosis and sarcopenia are associated with hepatic encephalopathy in patients with cirrhosis[J]. Hepatol Int, 2018, 12(4): 377-386. DOI: 10.1007/s12072-018-9875-9.
[22]	LATTANZI B, NARDELLI S, PIGLIACELLI A, et al. The additive value of sarcopenia, myosteatosis and hepatic encephalopathy in the predictivity of model for end-stage liver disease[J]. Dig Liver Dis, 2019, 51(11): 1508-1512. DOI: 10.1016/j.dld.2019.09.004.
[23]	TSIEN C, DAVULURI G, SINGH D, et al. Metabolic and molecular responses to leucine-enriched branched chain amino acid supplementation in the skeletal muscle of alcoholic cirrhosis[J]. Hepatology, 2015, 61(6): 2018-2029. DOI: 10.1002/hep.27717.
[24]	KUMAR A, DAVULURI G, SILVA R, et al. Ammonia lowering reverses sarcopenia of cirrhosis by restoring skeletal muscle proteostasis[J]. Hepatology, 2017, 65(6): 2045-2058. DOI: 10.1002/hep.29107.
[25]	KAPOOR B, KAPOOR D, GAUTAM S, et al. Dietary Polyunsaturated Fatty Acids (PUFAs): Uses and potential health benefits[J]. Curr Nutr Rep, 2021, 10(3): 232-242. DOI: 10.1007/s13668-021-00363-3.
[26]	ALMASUD AA, GILES KH, MIKLAVCIC JJ, et al. Fish oil mitigates myosteatosis and improves chemotherapy efficacy in a preclinical model of colon cancer[J]. PLoS One, 2017, 12(8): e0183576. DOI: 10.1371/journal.pone.0183576.
[27]	YOUNOSSI ZM, COREY KE, LIM JK. AGA clinical practice update on lifestyle modification using diet and exercise to achieve weight loss in the management of nonalcoholic fatty liver disease: expert review[J]. Gastroenterology, 2021, 160(3): 912-918. DOI: 10.1053/j.gastro.2020.11.051.
[28]	GATINEAU E, POLAKOF S, DARDEVET D, et al. Similarities and interactions between the ageing process and high chronic intake of added sugars[J]. Nutr Res Rev, 2017, 30(2): 191-207. DOI: 10.1017/S0954422417000051.
[29]	van DRONKELAAR C, van VELZEN A, ABDELRAZEK M, et al. Minerals and sarcopenia; the role of calcium, iron, magnesium, phosphorus, potassium, selenium, sodium, and zinc on muscle mass, muscle strength, and physical performance in older adults: A systematic review[J]. J Am Med Dir Assoc, 2018, 19(1): 6-11. e3. DOI: 10.1016/j.jamda.2017.05.026.