In Vitro and in Vivo Models of Non-Alcoholic Fatty Liver Disease (NAFLD)
<p>Schematic drawing of the molecular mechanisms involved in the development and progression of non-alcoholic fatty liver disease (NAFLD). The risk factors such as being overweight, visceral adiposity, adipocytokines may increase the flow of free fatty acids (FFAs) to the liver. Alterations of intestinal microbiota and increased permeation of bacterial endotoxins, from the gut may activate Toll-like receptor signaling cascades and lead to a M1 polarization of macrophages (e.g., of Kupffer cells and infiltrating macrophages). All these events (e.g., increased FFAs, adipocytokines, endotoxins, insulin resistance, macrophage polarization) may lead to the development of NAFLD. (Modified from Krawczyk <span class="html-italic">et al.</span> [<a href="#b4-ijms-14-11963" class="html-bibr">4</a>]).</p> ">
<p>(<b>A</b>) Representative photographs of a lean (C57BL/6) and an ob/ob mouse, as well as (<b>B</b>) representative photomicrographs of liver sections stained with hematoxylin and eosin (200×).</p> ">
<p>Effect of feeding a Western-style diet on the liver. Representative photomicrographs of hematoxylin and eosin staining of liver sections (200×) of mice fed with control or Western-style diet for 6 weeks.</p> ">
<p>Schematic drawing of co-culture model (as used by Spruss <span class="html-italic">et al.</span> [<a href="#b88-ijms-14-11963" class="html-bibr">88</a>]).</p> ">
Abstract
:1. Introduction
2. Histopathology and Pathogenesis of NAFLD
3. Animal Models of NAFLD
4. Genetic Rodent Models of NAFLD
4.1. Ob/ob, db/db and Obese (fa/fa) Zucker Rat
4.2. Agouti Gene [KK-Ay/a]
4.3. Melanocortin 4 Receptor (MC4R)
4.4. Sterol Regulator Element-Binding Protein 1c (SREBP)
5. Dietary Rodent Models of NAFLD
5.1. Methionine- and Choline-Deficient (MCD) Diet
5.2. High Fat Diet (HFD)
5.3. Fructose-Rich Diets
5.4. Western-Style or Fast Food Diet: Combination of Fat and Sugar
5.5. “Non-rodent” Animal Models of NAFLD
5.6. In Vitro Models for NAFLD
5.7. Co-Culture Model: Interaction of RAW 264.7 Macrophages and AML-12 Cells
5.8. Three-Dimensional Cell Culture Model
6. Conclusions
Acknowledgments
Abbreviations
NAFLD | non-alcoholic fatty liver disease |
NFκB | nuclear factor kappa B |
ROS | reactive oxygen species |
TNFα | tumor necrosis factor α |
TG | triglycerides |
IL-6 | interleukin 6 |
MCD | methionine- and choline-deficient |
MC4R | melanocortin 4 receptor |
HFD | high-fat diet |
SREBP1 | sterol regulator element-binding protein 1c |
HFCS | high fructose corn syrup |
Conflict of Interest
References
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Ingredients | g/100 g diet | Ingredients | g/100 g diet |
---|---|---|---|
Casein | 20.0 | Vitamin mixture | 1 |
DL methionine | 0.3 | Choline bitartrate | 0.2 |
Corn strach | 15.0 | Corn oil | 5 |
Sucrose | 48.7 | Sodium cholate | 0.3 |
Cellulose powder | 5 | Cholesterol | 1 |
Mineral mixture | 3.5 |
Control diet | % of energy from Nutrients | Western style diet | % of energy from Nutrients |
---|---|---|---|
Total sugars | 23.3 | Fructose | 50 |
Starch | 39 | Glucose | 5 |
Protein | 11 | Starch | 5 |
Fat | 24 | Protein | 15 |
Cholesterol | 0.2 | ||
Fat | 25 |
In vitro models | Cell lines | Pros | Cons |
---|---|---|---|
Primary cell cultures | Hepatocytes from NAFLD patients/rodents Kupffer cells/stellate cells/iNKT cells from human patients/rodents | Mimic in vivo settings | Isolation problems Ethical issues Varying reproducibility in experiments Limited culture time |
Immortalized cell lines | RAW 264.7, AML-12, J774A, HepG2, HuH7, H4IIE, H4IIEC3, PAV-1, LX2 | Continuous growth Easy to culture Stable phenotype | Expression of several enzymes and nuclear factors alter according to the immortalization method |
Co-culture models | RAW 264.7 and AML-12 Human hepatocytes and adipocytes | Mimic in vivo liver architecture Important tools in cellular cross talk studies | Difficult to cultivate |
3D cultures | H35 rat hepatoma cell line | Mimic in vivo liver architecture Liver specific differentiation and function Tools for transcriptional regulation studies | Difficult to cultivate |
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Kanuri, G.; Bergheim, I. In Vitro and in Vivo Models of Non-Alcoholic Fatty Liver Disease (NAFLD). Int. J. Mol. Sci. 2013, 14, 11963-11980. https://doi.org/10.3390/ijms140611963
Kanuri G, Bergheim I. In Vitro and in Vivo Models of Non-Alcoholic Fatty Liver Disease (NAFLD). International Journal of Molecular Sciences. 2013; 14(6):11963-11980. https://doi.org/10.3390/ijms140611963
Chicago/Turabian StyleKanuri, Giridhar, and Ina Bergheim. 2013. "In Vitro and in Vivo Models of Non-Alcoholic Fatty Liver Disease (NAFLD)" International Journal of Molecular Sciences 14, no. 6: 11963-11980. https://doi.org/10.3390/ijms140611963