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Fatty acid-induced toxicity and neutral lipid accumulation in insulin-producing RINm5F cells
Anna Karenina Azevedo-Martins1, Ariana Pereira Monteiro, Camila Lopes Lima
1Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, Av. Prof. Lineu Prestes, 1524, CEP: 05508-900. Butantan, São Paulo, Brazil. akam@icb.usp.br
Abstract:
Fatty acids have been shown to cause death of rat and human primary pancreatic beta cells and of insulin-producing cell lines. These studies focused mainly on saturated and monounsaturated FA such as palmitic, stearic and oleic acids. In this study, we have performed a comparison of the toxicity of a wider range of FA. The toxicity of different FA to insulin-producing RINm5F cells was assessed by flow cytometry measuring loss of plasma membrane integrity and increase in DNA fragmentation. Additionally, the FA induced neutral lipid accumulation and the FA composition were determined. Palmitic, linoleic, gamma-linolenic, oleic, stearic, and eicosapentaenoic acid caused DNA fragmentation of insulin-producing RINm5F cells. Loss of membrane integrity was mainly caused by linoleic and gamma-linolenic acid. There was no correlation between cytotoxicity and the abundance of the FA in the cells as determined by HPLC analysis. Taken as whole, the toxic effect of the FA on insulin-producing RINm5F cells varied irrespective of the chain length and the degree of unsaturation. In these cells PA and LA exhibited the highest toxicity, whereas AA was not toxic. In addition, the toxicity of most tested FA was inversely related to low NLA, except for AA and EPA. The results of this study contribute to the understanding of the role of FA in the impairment of pancreatic beta cell function that occurs in type 2 diabetes and obesity.
Insights
Fatty acids (FA) show varying toxicity to insulin-producing cells. Palmitic and linoleic acids were most toxic, impacting cell function relevant to type 2 diabetes and obesity.
Area of Science:
- Cell Biology
- Metabolic Research
- Toxicology
Background:
- Fatty acids (FA) are implicated in pancreatic beta cell death.
- Previous research focused on saturated and monounsaturated FA.
- Understanding diverse FA toxicity is crucial for metabolic disease research.
Purpose of the Study:
- To compare the toxicity of a wider range of FA on insulin-producing cells.
- To investigate the relationship between FA composition, lipid accumulation, and cytotoxicity.
- To elucidate FA roles in pancreatic beta cell dysfunction in type 2 diabetes and obesity.
Main Methods:
- Assessed FA toxicity in RINm5F cells using flow cytometry.
- Measured plasma membrane integrity and DNA fragmentation.
- Determined FA-induced neutral lipid accumulation and cellular FA composition via HPLC.
Main Results:
- Palmitic, linoleic, gamma-linolenic, oleic, stearic, and eicosapentaenoic acids induced DNA fragmentation.
- Linoleic and gamma-linolenic acids primarily caused membrane integrity loss.
- Toxicity varied irrespective of FA chain length or unsaturation; palmitic and linoleic acids were most toxic.
Conclusions:
- FA toxicity to insulin-producing cells is diverse and not solely dependent on chain length or saturation.
- Palmitic acid and linoleic acid exhibit significant cytotoxicity in RINm5F cells.
- Findings contribute to understanding FA's role in pancreatic beta cell dysfunction in type 2 diabetes and obesity.