Metabolic diseases such as diabetes, obesity, non-alcoholic fatty liver disease, and dyslipidaemias are major health challenges worldwide. Research into these conditions requires robust models that replicate aspects of human physiology, enabling the study of nutrient processing, energy metabolism, and drug effects. Immortalised cell lines provide a reproducible and ethical solution, bridging gaps between primary tissue experiments and clinical trials.
By mimicking organ-specific metabolic processes, cell lines have become central to exploring how nutrients and drugs are absorbed, stored, and utilised. This article examines ten of the most widely used lines in the context of metabolism and nutrition.
HeLa Cells and Cellular Energy Metabolism
Though primarily associated with cancer biology, HeLa cells have also contributed extensively to our understanding of basic cellular metabolism. Their high proliferation rate and metabolic reprogramming make them a classic model for studying the “Warburg effect”, where tumour cells preferentially utilise glycolysis over oxidative phosphorylation, even in the presence of oxygen.
In nutritional research, HeLa cells have been used to:
- Examine glucose uptake pathways, clarifying how cancer cells adapt to nutrient availability.
- Study mitochondrial function, particularly under stress conditions such as hypoxia.
- Investigate nutrient–gene interactions, including how vitamins and minerals influence chromosomal stability.
By highlighting metabolic flexibility, HeLa cells have provided insights into how tumours manipulate nutrient pathways, with broader implications for understanding systemic metabolic disorders.
HEK293 and Genetic Regulation of Metabolism
HEK293 cells, derived from embryonic kidney tissue, are widely used for metabolic studies requiring genetic manipulation. Their high transfection efficiency allows researchers to express or silence genes involved in nutrient transport and metabolic signalling.
Applications include:
- Transporter studies, such as sodium-glucose linked transporters or amino acid carriers.
- Hormone receptor signalling, including insulin and leptin pathways.
- Gene editing models, where metabolic regulators can be manipulated using CRISPR-Cas9.
By enabling the study of genetic regulation in nutrient metabolism, HEK293 provides a versatile system to link molecular changes with metabolic outcomes.
CHO Cells and Biomanufacturing of Metabolic Hormones
In addition to their industrial use in protein production, CHO cells are central to research into hormones and enzymes that regulate metabolism. Their ability to produce recombinant proteins with human-like post-translational modifications makes them a preferred host for studying metabolic regulators.
CHO-based systems have been used to:
- Produce recombinant insulin and insulin analogues for diabetes therapy.
- Generate enzymes for lysosomal storage disorders affecting metabolism.
- Investigate the glycosylation of metabolic hormones and its impact on activity.
Thus, CHO cells are both producers of metabolic therapies and contributors to research into how structural variations influence hormonal function.
SH-SY5Y and Neuronal Metabolism
Neurons have unique metabolic requirements, and the SH-SY5Y neuroblastoma line provides an adaptable model for exploring neuronal energy utilisation. By differentiating into neuron-like cells, SH-SY5Y enables researchers to investigate how brain metabolism relates to nutrition and disease.
Key applications include:
- Glucose metabolism in neurons, critical for understanding diabetic neuropathy.
- Mitochondrial dysfunction, which links to neurodegenerative diseases and metabolic stress.
- Neurotransmitter synthesis, influenced by amino acid availability and nutritional states.
By replicating aspects of neuronal metabolism, SH-SY5Y bridges neurological and metabolic research, highlighting how diet and systemic metabolism influence brain health.
MCF7 and Hormonal Regulation of Metabolism
Hormones profoundly influence metabolic balance, and MCF7 cells, which express oestrogen receptors, offer an avenue to study endocrine–metabolic links. Beyond their cancer relevance, MCF7 cells help clarify how hormonal fluctuations affect energy utilisation and nutrient storage.
Research with MCF7 has contributed to:
- Understanding oestrogen’s role in glucose metabolism, particularly its effects on insulin sensitivity.
- Exploring lipid storage pathways, influenced by endocrine signalling.
- Investigating endocrine-disrupting chemicals, which can mimic hormones and alter metabolic balance.
These studies underscore the importance of hormonal control in metabolism, with implications for obesity and diabetes research.
THP1 and Immunometabolism
The immune system’s metabolic activity plays a crucial role in inflammation and systemic energy balance. THP1 cells, derived from monocytic leukaemia, provide a model for investigating “immunometabolism” — the intersection of immune activation and nutrient use.
Applications include:
- Studying metabolic reprogramming in macrophages, where glucose and lipid utilisation change during inflammation.
- Evaluating how nutrients regulate cytokine production, linking diet to immune responses.
- Testing drugs for effects on inflammatory metabolic pathways, relevant to metabolic syndrome.
THP1 cells highlight how immune responses and metabolism are intertwined, particularly in obesity-related chronic inflammation.
A2780 and Chemotherapy–Metabolism Interactions
While primarily used in oncology, A2780 ovarian carcinoma cells also inform metabolic research by revealing how chemotherapy interacts with nutrient pathways. Tumour metabolism often overlaps with systemic metabolic disorders, making A2780 relevant for dual perspectives.
Research has shown:
- Chemotherapy-induced metabolic stress, where drugs alter glucose and lipid metabolism.
- Interactions between diet and drug responses, particularly nutrient availability influencing therapy efficacy.
- Metabolic resistance mechanisms, where tumours reprogram pathways to survive drug exposure.
These findings emphasise the role of metabolic context in cancer therapy, with implications for personalised nutrition and treatment strategies.
HL-60 and Energy Demands of Differentiation
The promyelocytic HL-60 line, capable of differentiating into granulocytes or monocytes, provides a platform to study metabolic changes during immune cell development. Differentiation requires shifts in energy use, linking nutrient metabolism to haematopoietic function.
HL-60 has been used to:
- Study glycolytic versus oxidative metabolism during differentiation.
- Investigate the role of fatty acid oxidation in immune cell survival.
- Test metabolic toxins that impair blood cell development.
By connecting energy metabolism to cellular fate, HL-60 helps clarify how nutritional states and metabolic disruptions affect immune development.
Caco-2 and Nutrient Absorption
Perhaps the most famous nutritional model, Caco-2 cells are indispensable for studying intestinal absorption. When cultured, they develop enterocyte-like features, replicating the human intestinal barrier.
Applications are extensive, including:
- Drug absorption testing, where permeability predicts oral bioavailability.
- Nutrient transport studies, for vitamins, minerals, and peptides.
- Interactions between diet and xenobiotics, including how food affects drug uptake.
Caco-2 cells form a bridge between diet and pharmacology, offering insights into how the gut regulates nutrient availability and systemic metabolism.
HepG2 and Hepatic Metabolism
As the liver is central to metabolism, HepG2 cells have become one of the most widely used models in nutritional and metabolic research. Derived from hepatocellular carcinoma, they retain many liver-specific functions, making them ideal for exploring xenobiotic and nutrient metabolism.
They are employed to:
- Study lipid metabolism, particularly pathways involved in fatty liver disease.
- Investigate carbohydrate metabolism, including glucose storage and release.
- Model xenobiotic interactions, where drugs or toxins affect liver energy pathways.
Although they lack the complete enzymatic profile of primary hepatocytes, HepG2 cells remain indispensable for large-scale, reproducible studies of hepatic metabolism.
Conclusion
Metabolic disease research relies on a mosaic of immortalised cell lines, each contributing unique insights into nutrient absorption, energy regulation, and systemic balance. HeLa clarified tumour metabolism, HEK293 revealed genetic control of transporters, and CHO produced metabolic hormones. SH-SY5Y connected brain metabolism to nutrition, MCF7 highlighted hormonal influences, and THP1 exposed links between immunity and metabolism. A2780 illuminated chemotherapy–nutrient interactions, HL-60 showed energy shifts during immune differentiation, Caco-2 replicated gut absorption, and HepG2 captured liver metabolism.
Together, these models form a toolkit for exploring the complexities of nutrition and metabolic disease. While they cannot replace the intricacies of whole-body physiology, they provide reproducible systems that accelerate discoveries, shape dietary guidelines, and guide therapeutic strategies for metabolic health.
