info@biomedres.us   +1 (502) 904-2126   One Westbrook Corporate Center, Suite 300, Westchester, IL 60154, USA   Site Map
ISSN: 2574 -1241

Impact Factor : 0.548

  Submit Manuscript

Mini ReviewOpen Access

Application of Animal Models in MAFLD Volume 48- Issue 1

Li Yuxi1, Gao Linghuan2, Zhang Haizhu3 and Zhang Yuxin2*

  • 1School of Basic Medical Sciences North China University of Science and Technology, China
  • 2North China University of Science and Technology, China
  • 3Hebei Key Laboratory for Chronic Diseases, Tangshan Key Laboratory for Preclinical and Basic Research on Chronic Diseases, School of Basic Medical Sciences, North China University of Science and Technology, Tangshan, PR China

Received: January 03, 2022;   Published: January 18, 2023

*Corresponding author: Zhang Yuxin, North China University of Science and Technology, Caofeidian District, Tangshan City, Hebei Province: 063210, China

DOI: 10.26717/BJSTR.2023.48.007605

Abstract PDF

ABSTRACT

Abbreviations: MAFLD: Metabolic Dysfunction-Associated Fatty Liver Disease; NAFLD: Non-Alcoholic Fatty Liver Disease; NASH: Non-Alcoholic Steatohepatitis; ALM: Aberrant Lipid Metabolism; IR: Insulin Resistance; AGEs: Advanced Glycation End Product; HFD: High-Fat Diet; HCD: High-Cholesterol Diet; MCD: Methionine and Choline Deficiency; HFHF: High Fat High Fructose; CDAA: Choline-Deficient Amino Acid Diet; LDH: Lactate Dehydrogenase; LDL: Low-Density Lipoprotein

Mini Review

Metabolic dysfunction-Associated Fatty Liver Disease (MAFLD), formerly called non-alcoholic fatty liver disease (NAFLD), and its usually develop to non-alcoholic steatohepatitis (Nonalcoholic steatohepatitis, NASH). MAFLD is not a single disease entity, it belongs to the complication of metabolic syndrome, which is mainly responsible for liver damage, excluding excessive drinking and other clear interventions (such as viruses, drugs, and genetics) [1]. Different from alcoholic fatty liver disease and other toxic fatty liver disease are mainly in the peripheral lobular zone, MAFLD is a widespread diffuse hepatocytic fat change. Pathological manifestations of the liver is large and soft, under the light microscope, it can be observed that parenchyma cell fatty degeneration, nuclear displacement; mesenchymal proliferations in portal area, immune cell infiltration landscapes; liver lobular area involvement, sometimes visible central vein deviation. MAFLD is mainly divided into four types of pathological changes, Simple steatosis Lobular inflammation, Ballooning and Fibrosis, Ballooning is a important sign of NASH [2]. These pathologies are not necessarily progressive, and two lesions may coexist [3] (Figure 1).

Figure 1 The pathophysiology of MAFLD [3].

biomedres-openaccess-journal-bjstr

Pathogenesis of MAFLD

The pathogenesis of MAFLD is not clear, and it is generally believed to be mainly related to the accumulation of Aberrant lipid metabolism (ALM), insulin resistance (IR), and advanced glycation end product (AGEs) caused by diabetes Some studys suggested that these pathological manifestations are all tissue-specific phenotypes of the same pathophysiological processes [4].

Selection of the Animal Models

In vitro models of MAFLD are HepG2 cells, LX2 cells, macrophages, primary hepatocytes, etc. Animal models mainly include genetic modification type, diet induced type, chemical drug-induced type, and Complex models. The method is mostly used by gavage, intraperitoneal injection and intravenous injection. The models selected took abnormal glucose and lipid metabolism as the main phenotype, roughly including the following several.

Genic Mutation Type

Both ob/ob mice and db/db mice are genetically altered mice associated with leptin epigenetics, and ob/ob mice are a leptin synthesis disorder due to the leptin-encoding gene mutations, and ob/ob mice generally do not have spontaneous inflammation and fibrosis. The db/db mice are leptin receptor knockout mice, homozygous to fertility, and db/db mice are divided into C57BL/6 and BKS types, with survival cycle, blood glucose, liver injury and kidney injury under different genetic backgrounds [5]. Other transgenic mice include foz/foz, ApoE-/-, Srebp-1c transgenic mice, and Nlrp3 transgenic mice [6]. In order to shorten the moldmaking cycle and accelerate the progression of the disease [7], the combined diet induction is generally used as a MAFLD model [8,9]. In addition, KKAY mice are a mildly obese type 2 diabetic animal, with a significant increase in blood glucose and blood insulin levels, which can induce non-alcoholic fatty liver disease [10].

Diet-Induced Type

Diet induction includes high-fat diet (high fat diet, HFD), fat energy supply ratio 45% -70% kcal; high-cholesterol diet (HCD) 1.25% cholesterol + 0.5% cholate; high-fat and high-cholesterol diet (cholesterol content 0.5%); methionine and choline deficiency diet (MCD); high-fat and high-fructose diet (high fat high fructose, HFHF) fed for 60 days [11], choline-deficient amino acid diet (CDAA), etc.

Chemical Drug-Induced Type

Chemical drugs induce the common streptozotocin STZ that is intraperitoneally injected into SD rats [12], which often causes kidney damage in addition to causing liver damage.

Complex Model

Composite model refers to the selection of two or more ways induced metabolic correlation fatty liver model, such as diet induced and (or) combined chemical drugs applied to transgenic mice, common means are HFHF (high fat high fructose) diet, MCD (methionine choline deficiency) diet, increased intake of trans fatty acids, injection of bacterial endotoxin (LPS) cause «secondary hit», such as high fat diet combined with STZ induction[13,14]can induce MAFLD on the basis of NASH [15].

Diagnosis of MAFLD

CT and MRI on imaging examination can assess liver size, exclude other space-occupying lesions, and ultrasound transient elastography is combined with an XL probe [16]. Liver tissue biopsy is the most diagnostic significance, but because the biopsy is invasive and prone to bias due to improper collection site [17]. LDH (lactate dehydrogenase), GSH (also prototype glutathione), LDL (low-density lipoprotein), etc. In addition, some commercial kits, such as SteatoTest detection biomarkers, ActiTest, NashTest-2 and FibroTest, have been verified to be used for the diagnosis of liver fat change, fatty inflammation and fibrosis [18].

Discussion

Due to the individual differences between rodent, there are all individual cases of unsuccessful example, how to verify is a inescapable problem. In addition to biochemical indexes such as blood glucose and LDL, liver tissue biopsy is the most standard and effective verification method. In addition, because mice are very prone to hepatitis and the disease spreads quickly, it is easy to interfere with subsequent experiments (especially in inflammatory signaling pathway). Hence, pay more attention to the cleanliness of the feeding environment is necessary.

Acknowledgements

This work was supported by the Postgraduate Research Training Program of Hebei Province [CXZZSS2023076].

References

  1. Lin S, Huang JF, Wang MF (2020) Comparison of MAFLD and NAFLD diagnostic criteria in real world. Liver Int 40(9): 2082-2089.
  2. Antunes C, Azadfard M, Hoilat GJ (2021) Fatty Liver. [M]. StatPearls.
  3. Friedman SL, Neuschwander Tetri BA, Rinella M (2018) Mechanisms of NAFLD development and therapeutic strategies. Nat Med 24 (7): 908-922.
  4. Thomas MC, Brownlee M, Susztak K (2015) Diabetic kidney disease. Nat Rev Dis Primers 30(1): 15018.
  5. Wu Jing, Wang Huamin, Li Jing, Men Xiuli (2013) Laboratory application of db/db mice. Advances in Physiological Sciences

44(01): 12-18.

  1. Kawamura, Satoshi (2022) Inhibiting SCAP/SREBP exacerbates liver injury and carcinogenesis in murine nonalcoholic steatohepatitis. J Clin Invest 132(11): e151895.
  2. Xu B, Jiang MZ, Chu Y (2018) Gasdermin D plays a key role as a pyroptosis executor of non-alcoholic steatohepatitis in humans and mice. J Hepatol 68(4): 773-782.
  3. Koh EH, Yoon JE, Ko MS (2021) Sphingomyelin synthase 1 mediates hepatocyte pyroptosis to trigger non-alcoholic steatohepatitis. Gut 70(10): 1954-1964.
  4. Cannito S, Morello E, Bocca C (2017) Microvesicles released from fat-laden cells promote activation of hepatocellular NLRP3 inflammasome: A pro-inflammatory link between lipotoxicity and non-alcoholic steatohepatitis. PLoS One 12(3): e0172575.
  5. Sakuma, Takafumi (2022) A diet-induced murine model for non-alcoholic fatty liver disease with obesity and insulin resistance that rapidly develops steatohepatitis and fibrosis. Lab Invest 102(10): 1150-1157.
  6. Chyau, Charng-Cherng (2020) Antrodan Alleviates High-Fat and High-Fructose Diet-Induced Fatty Liver Disease in C57BL/6 Mice Model via AMPK/Sirt1/SREBP-1c/PPAR γ Int J Mol Sci 21(1): 360.
  7. Zhao M, Qin JP, Shen WT (2021) Bilobalide Enhances AMPK Activity to Improve Liver Injury and Metabolic Disorders in STZ-Induced Diabetes in Immature Rats via Regulating HMGB1/TLR4/NF-κB Signaling Pathway. Biomed Res Int, pp. 8835408.
  8. Zhao S, Song TY, Gu Y (2021) Hydrogen Sulfide Alleviates Liver Injury Through the S-Sulfhydrated-Kelch-Like ECH-Associated Protein 1/Nuclear Erythroid 2-Related Factor 2/Low-Density Lipoprotein Receptor-Related Protein 1 Pathway. Hepatology 73(1): 282-302.
  9. Yang MM, Cui YX, Song J (2021) Mesenchymal stem cell-conditioned medium improved mitochondrial function and alleviated inflammation and apoptosis in non-alcoholic fatty liver disease by regulating SIRT1. Biochem Biophys Res Commun (546): 74-82.
  10. Bessone F, Razori MV, Roma MG (2019) Molecular pathways of nonalcoholic fatty liver disease development and progression. Cell Mol Life Sci 76(1): 99-128.
  11. Mikolasevic I, Orlic L, Franjic N (2016) Transient elastography (FibroScan) with controlled attenuation parameter in the assessment of liver steatosis and fibrosis in patients with nonalcoholic fatty liver disease - where do we stand? World J Gastroenterol 22(32): 7236-7251.
  12. Cariou B, Byrne CD, Loomba R (2021) Nonalcoholic fatty liver disease as a metabolic disease in humans: A literature review. Diabetes Obes Metab 23(5): 1069-1083.
  13. Bril F, McPhaul MJ, Caulfield MP (2019) Performance of the SteatoTest, ActiTest, NashTest and FibroTest in a multiethnic cohort of patients with type 2 diabetes mellitus. J Invest Med 67(2): 303-311.