Cell Culture Models of Fatty Acid Overload: Problems and Solutions
Open accessAbstract
High plasma levels of fatty acids occur in a variety of metabolic diseases. Cellular effects of fatty acid overload resulting in negative cellular responses (lipotoxicity) are often studied in vitro, in an attempt to understand mechanisms involved in these diseases. Fatty acids are poorly soluble, and thus usually studied when complexed to albumins such as bovine serum albumin (BSA). The conjugation of fatty acids to albumin requires care pertaining to preparation of the solutions, effective free fatty acid concentrations, use of different fatty acid species, types of BSA, appropriate controls and ensuring cellular fatty acid uptake. This review discusses lipotoxicity models, the potential problems encountered when using these cellular models, as well as practical solutions for difficulties encountered.
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In vitro models allow precise and independent control of individual variables (fatty acid concentration/composition, glucose, insulin, oxygen, cytokines, co-culture configurations, therapeutic agents) in a way virtually impossible in whole organisms.
“A key advantage of in vitro models is the ability to precisely and independently control individual variables in a way that is virtually impossible in studies on whole organisms [29,55].”
From The HepG2 Cell Line as a Model for Studying Metabolic Dysfunction-Associated Steatotic Liver Disease (2026) · cites this paper as [55]
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Experimental — accuracy not yet measuredIn healthy human plasma, the FFA:BSA molar ratio is typically in the range of 1:1-3:1, whereas in pathological conditions it may exceed 5:1-6:1.
“In healthy human plasma, the FFA:BSA molar ratio is typically in the range of 1:1–3:1, whereas in pathological conditions it may exceed 5:1–6:1 [55,145].”
From The HepG2 Cell Line as a Model for Studying Metabolic Dysfunction-Associated Steatotic Liver Disease (2026) · cites this paper as [55]
Section 5 states that healthy human serum FA:BSA ratios range from 1:1 to 3:1 and can be higher than 5:1 in disease states. It does not specify that they may exceed 6:1, so the upper threshold in the claim is not established by this passage. (LLM, conf=0.86)
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References 148 · Cited by 167
Research works printed but not linked: 1
- [142]Gómez-Lechón MJ Donato MT Martíez-Romero A Jiménez N Castell JV O’Connor JE A human hepatocellular in vitro model to investigate steatosis Chem. Biol. Interact 165 2007 106 116 17188672
- Authors
- Alsabeeh, N., Chausse, B., Kakimoto, P. A., Kowaltowski, A. J., & Shirihai, O.
- Affiliations
- Boston University (US)
- Universidade de São Paulo (BR)
- University of California, Los Angeles (US)
- Corresponding author
- Kowaltowski, Alicia J.
- Venue
- Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids
- Publisher
- Elsevier BV
- Published
- 2018-02
- Volume
- 1863
- Issue
- 2
- Pages
- 143-151
- ISSN
- 1388-1981 (ISSN-L)
- PMC
- PMC5969525
- OpenAlex
- W2769288280
- Cited by
- 167
- References
- 148
- Citations by year
- 2026: 21 · 2025: 23 · 2024: 30 · 2023: 17 · 2022: 21 · 2021: 25 · 2020: 17 · 2019: 10 · 2018: 3
- FWCI
- 0.82
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids (acceptedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- NIH-NIDDK (5-R01DK099618-02)
- CEPID (2013/07937-8)
- FAPESP (PD 2015/07670-7, 2015/25862-0)
- CNPq
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diet, Metabolism, and Disease
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
- Keywords
- fatty acid overload, lipotoxicity, cell culture model, bovine serum albumin, hypertriglyceridemia, metabolic disorders
- MeSH terms
- Animals, Cattle, Fatty Acids, Humans, Models, Biological, Serum Albumin, Bovine, Cell Culture Techniques, Lipid Metabolism Disorders
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