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Advancing MASLD & MASH Research: Tools & Strategies for Metabolic Dysfunction in Steatotic Liver Diseases
Advancing MASLD & MASH Research: Tools & Strategies for Metabolic Dysfunction in Steatotic Liver Diseases
Article from 2024-08-28
Welcome to our series on advancing metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH) research by targeting metabolic factors in steatotic liver diseases (SLDs). In this series, each post covers a specific area related to metabolic dysfunction in steatotic liver diseases, creating a guide to the strategies and research tools used to study metabolic dysfunction in these conditions.
The full series covers:
- Advancing MASLD & MASH Research: An Introduction
- Advancing MASLD & MASH Research: Targeting De Novo Lipogenesis & Insulin Resistance
- Advancing MASLD & MASH Research: PPAR and FFAR Fatty Acid Signaling Pathways
- Advancing MASLD & MASH Research: The Roles of LXRs, FXRs, and GP-BAR1 in Metabolic Regulation
Discover products and resources that support your research by exploring these topics.
Understanding MASLD & MASH: An Introduction
Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as non-alcoholic fatty liver disease (NAFLD), is a complex and heterogenous spectrum of liver conditions.1 MASLD is characterized by abnormal accumulation of lipids in hepatocytes, a condition called hepatic steatosis.1 MASLD can progress to a more severe form known as metabolic dysfunction-associated liver steatohepatitis (MASH). In this stage, the liver undergoes sustained inflammation and cell injury.2 Without effective therapies that halt or reverse the progression of MASH, individuals with MASH are at risk of developing cirrhosis. Cirrhosis is a severe, progressive condition characterized by extensive liver fibrosis that may lead to loss of liver function.3
New Nomenclature for Fatty Liver Diseases
| | Fatty liver diseases have recently been renamed to better reflect the underlying metabolic origins of these diseases, rely on positive criteria instead of exclusion criteria for diagnosis, and avoid the use of stigmatizing terminology.4,5 |
We acknowledge the newly introduced terminology for fatty liver diseases and appreciate its significance. Adopting this new nomenclature across our company will be a gradual process. We are reviewing our existing literature and product categories to reflect the new terminology as appropriate.
The Difference Between MASLD and MASH
| MASLD | MASH |
| Metabolic dysfunction-associated steatotic liver | Metabolic dysfunction-associated steatohepatitis |
| A mild form of SLD where steatosis is present in the liver in the absence of liver injury or inflammation.6 | A more severe form of SLD marked by steatosis in the presence of sustained liver inflammation.7 |
| Typically non-progressive and relatively benign.6 | Can progress to more severe conditions like liver fibrosis and cirrhosis.8 |
Distinguishing MASLD from MASH is important as they have different outlooks and associated risks. Individuals with MASH are at risk of developing the more severe conditions such as cardiovascular disease, cancer, cirrhosis, and liver failure.9 Both MASLD and MASH are thought to be reversible, but when the disease has progressed to cirrhosis, transplantation may be the only option.
| | Accurate distinction between MASLD and MASH is critical for designing therapeutic strategies aimed at reducing the potential progression to more severe complications. |
There are Critical Needs for New Therapies
30% of the global population is affected by MASLD10 | MASLD-related mortality is increasing10 | There is only one FDA-approved therapy for MASH11 |
MASLD is the most common liver disease in the world, affecting an estimated 30% of the global population, with regional prevalences exceeding 40% in some areas.10,12 MASLD prevalence is increasing worldwide and coincides with rising incidences of obesity and diabetes.10 Accordingly, MASLD is closely associated with various metabolic risk factors, including obesity, dyslipidemia, and insulin resistance/type 2 diabetes.13,14
Until recently, there were no medication options for treating MASLD, and treatment strategies were focused on lifestyle modifications. In March 2024, the US FDA approved resmetirom for the treatment of MASH.11
MASLD Hallmarks
Hepatic steatosis is the hallmark of SLDs like MASLD and MASH (Figure 1). It is characterized by the intracellular accumulation of lipids, especially triglycerides (TGs), in the form of lipid droplets in hepatocytes.15 This accumulation results from excessive amounts of lipids, which is attributable to imbalances in fatty acid uptake, synthesis, export, and oxidation and is mediated by many underlying factors.16
Figure 1. Photomicrograph of hepatic steatosis revealing lipid accumulation in hepatocytes.
MASLD Pathogenesis
The development and progression of MASLD is influenced by a myriad of factors, including genetic and epigenetic, dietary and environmental, and metabolic factors, all contributing to its complexity.17 In accordance with its name, MASLD is closely associated with metabolic dysregulation associated with conditions such as obesity, insulin resistance and diabetes, dyslipidemia, and metabolic syndrome. Addressing underlying metabolic dysregulations is a key strategy for MASLD therapeutics.13,14
| | The development of hepatic steatosis is closely associated with obesity, insulin resistance and diabetes, dyslipidemia, and metabolic syndrome. These metabolic factors are valuable strategies for new therapeutic approaches in the treatment of MASLD. |
MASLD arises from imbalances in energy homeostasis stemming from altered glucose and lipid metabolism. Several dysregulations contribute to the accumulation of excess lipids in the liver, including de novo lipogenesis, increased lipolysis, and reduced fatty acid oxidation and lipid export (Figure 2).13,14,16 This results in hepatic lipid accumulation, which lead to hepatic steatosis.
Figure 2. Summary of pathways leading to hepatic lipid accumulation in MASLD. Figure modified from Meex, R.C.R. and Watt, M.J. Hepatokines: linking nonalcoholic fatty liver disease and insulin resistance. Nat. Rev. Endocrinol. 13(9), 509-520 (2017).18
Hepatic steatosis and its associated metabolic disturbances can have cascading effects in the liver. It impairs cellular signaling cascades that regulate metabolism and cell function and induces inflammation and cellular injury, collectively promoting liver damage and disease progression.19
Research Tools for Targeting Metabolic Pathways in MASLD
Therapeutic strategies that target metabolic disturbances in MASLD are aimed at reducing metabolic injury and stress. By targeting these metabolic processes, the subsequent hepatic steatosis, inflammation, and cellular damage they elicit can be reduced, potentially halting the progression of this condition.20
Essential Assay Kits for MASLD & MASH Research
Assays that measure the extent of liver injury by quantifying steatosis or measuring levels of widely used markers of liver damage are essential for MASLD research.
| Item No. | Product Name | Description |
| 10012643 | Steatosis Colorimetric Assay Kit | Detect excessive lipid accumulation in cells. |
| 700260 | Alanine Transaminase Colorimetric Activity Assay Kit | Measure ALT activity in serum, plasma, tissue samples, and cell lysates. |
| 701710 | Alkaline Phosphatase Colorimetric Activity Assay Kit | A colorimetric assay for the detection of ALP activity in plasma, serum, tissue samples, and cell lysates. |
| 701640 | Aspartate Aminotransferase Colorimetric Activity Assay Kit | Measure AST activity in serum, plasma, tissue samples, and cell lysates. |
| 501760 | Albumin (human) ELISA Kit | A competitive ELISA for the quantification of albumin. |
In conclusion, MASLD results from a complex interplay of metabolic factors that culminate in hepatic steatosis and potential progression to more severe forms of steatotic liver disease. As research continues, several key metabolic dysregulations have been implicated in MASLD pathogenesis, including de novo lipogenesis, insulin resistance, and lipid homeostasis.
Next Post:
Related Posts:
- Advancing MASLD & MASH Research: PPAR and FFAR Fatty Acid Signaling Pathways
- Advancing MASLD & MASH Research: The Roles of LXRs, FXRs, and GP-BAR1 in Metabolic Regulation
Products for MASLD & MASH Research
The products featured in this series are a snapshot of the comprehensive resources available from Cayman for MASLD and MASH research. Our full catalog contains a comprehensive range of biochemicals, proteins, antibodies, and assay kits to support MASLD and MASH research.
View all MASLD-related products
References
1. Syed-Abdul, M.M. Lipid metabolism in metabolic-associated steatotic liver disease (MASLD). Metabolites 14(1), 12 (2024).
2. Chan, W.-K., Chuah, K.-H., Rajaram, R.B., et al. Metabolic dysfunction-associated steatotic liver disease (MASLD): A state-of-the-art review. J. Obes. Metab. Syndr. 32(3), 197-213 (2023).
3. Acharya, P., Chouhan, K., Weiskirchen, S. et al. Cellular mechanisms of liver fibrosis. Front. Pharmacol. 12, 671640 (2021).
4. Rinella, M.E., Lazarus, J.V., Ratziu, V., et al. A multisociety Delphi consensus statement on new fatty liver disease nomenclature. Hepatology 78(6), 1966-1986 (2023).
5. Eslam, M., Sanyal, A.J., George, J., et al. MAFLD: A consensus-driven proposed nomenclature for metabolic associated fatty liver disease. Gastroenterology 158(7), 1999-2014.e1 (2020).
6. Armandi, A. and Bugianesi, E. Dietary and pharmacological treatment in patients with metabolic-dysfunction associated steatotic liver disease. Eur. J. Intern. Med. 122, 20-27 (2024).
7. Ghazanfar, H., Javed, N., Qasim, A., et al. Metabolic dysfunction-associated steatohepatitis and progression to hepatocellular carcinoma: A literature review. Cancers (Basel) 16(6), 1214 (2024).
8. Paklar, N., Mijic, M., and Filipec-Kanizaj, T. The outcomes of liver transplantation in severe metabolic dysfunction-associated steatotic liver disease patients. Biomedicines 11(11), 3096 (2023).
9. Westfall, E.C., Jeske, R., and Bader, A.R. Nonalcoholic fatty liver disease: Common questions and answers on diagnosis and management. Am. Fam. Physician 102(10), 603-612 (2020).
10. Teng, M.L., Ng., C.H., Huang, D.Q., et al. Global incidence and prevalence of nonalcoholic fatty liver disease. Clin. Mol. Hepatol. 29(Suppl), S32-S42 (2023).
11. Petta, S., Targher, G., Romeo, S., et al. The first MASH drug therapy on the horizon: Current perspectives of resmetirom. Liver Int. 44(7), 1526-1536 (2024).
12. Cotter, T.G. and Rinella, M. Nonalcoholic fatty liver disease 2020: The state of the disease. Gastroenterology 158(7), 1851-1864 (2020).
13. Schuppan, D. and Schattenberg, J.M. Non-alcoholic steatohepatitis: Pathogenesis and novel therapeutic approaches. J. Gastroenterol. Hepatol. 28(Suppl1), 68-76 (2013).
14. Godoy-Matos, A.F., Silva Júnior, W.S., and Valerio, C.M. NAFLD as a continuum: From obesity to metabolic syndrome and diabetes. Diabetol. Metab. Syndr. 12, 60 (2020).
15. Alamri, H., Patterson, N.H., Yang, E., et al. Mapping the triglyceride distribution in NAFLD human liver by MALDI imaging mass spectrometry reveals molecular differences in micro and macro steatosis. Anal. Bioanal. Chem. 411(4), 885-894 (2019).
16. Chiappini, F., Coilly, A., Kadar, H., et al. Metabolism dysregulation induces a specific lipid signature of nonalcoholic steatohepatitis in patients. Sci. Rep.7, 46658 (2017).
17. Buzzetti, E., Pinzani, M., and Tsochatzis, E.A. The multiple-hit pathogenesis of non-alcoholic fatty liver disease (NAFLD). Metabolism 65(8), 1038-1048 (2016).
18. Meex, R.C.R. and Watt, M.J. Hepatokines: Linking nonalcoholic fatty liver disease and insulin resistance. Nat. Rev. Endocrinol. 13(9), 509-520 (2017).
19. Chakravarthy, M.V. and Neuschwander-Tetri, B.A. The metabolic basis of nonalcoholic steatohepatitis. Endocrinol. Diabetes Metab. 3(4), e00112 (2020).
20. Tacke, F., Puengel, T., Loomba, R., et al. An integrated view of anti-inflammatory and antifibrotic targets for the treatment of NASH. J. Hepatol. 79(2), 552-566 (2023).
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