Oleic Acid Protected Pancreatic β‐Cell Against Saturated Fatty Acid Induced Lipotoxicity
Authors: Liu Xiaohong , Chen Xuanming , Li Linzhao , Luo Ruixi , Long Dan , Lu Yanrong , Chen Younan 
Published: June 2021

Background

The loss of functional pancreatic β‐cell has played a critical role in the development of type 2 diabetes (T2DM). Chronic exposure to high free fatty acids (FFAs) in the context of hyperlipidemia or ectopic deposition of fat in pancreas is recognized as a causal factor for β‐cell dysfunction in T2DM. It is widely accepted that saturated FFAs, such as palmitic acid (PA), are responsible for β‐cell apoptosis, however, unsaturated FFAs, such as oleic acid (OA), are reported unharmful. In the present study, we investigated the PA induced intercellular toxicity and whether monounsaturated OA could counteract these detrimental effects when combined with PA. This work will give insights to the dietary therapy in T2DM.

Methods

Rat insulinoma cell line INS‐1E were incubated with 0.2 mM PA, 0.2 mM OA or the combination for 24 h. Cell viability was determined by CCK8 assay, and cell apoptosis was measured by flow cytometry, respectively. Western blot were performed to detect endoplasmic reticulum stress (ER stress) related proteins. The effects of OA on thapsigargin (Thp) induced ER stress of INS‐1E β‐cells were evaluated by CCK8 assay. The 24 h chronic insulin secretion was measured by Elisa.

Result

1) PA deteriorated cell viability of INS‐1E β‐cells in dose and time dependent manner. PA of 0.2 mM has remarkably decreased the cell viability (60%) compared to controls after 24 h incubation. Stimulation with OA showed no effect on cell viability but the combination of OA and PA robustly restored the viability to normal level. The proportion of apoptotic cells was increased to 43.5% after PA challenge for 24 h, whereas cosupplementation of OA dramatically rescued the INS‐1 cells from cell death. Consistently, OA alone has not induced cell apoptosis. 2) To explore the mechanism responsible for the protective role of OA, we focused on ER stress. OA alleviated PA‐triggered ER stress, evidenced by remarkably decreased protein levels of ER stress markers (CHOP and p‐PERK). Interestingly, classical ER stressor Thp declined the viability of INS‐1 cells, while OA was able to abrogate this effect, confirming its protective role in ER stress. 3) Furthermore, insulin secretion was increased when INS‐1E cells were incubated with PA plus OA, in comparison to either OA or PA alone, suggesting the trophic effect of combination treatment on the function of β‐cells. 4) On the other hand, withdrawal of PA after 24 h exposure, then addition of OA for a further 24 h showed no protective effects on cell viability. The time course showed that withdrawal of 1.0 mM PA after 6 h, 8h and 10 h exposure, and addition of OA for a further 18 h, 16 h and 14 h respectively, earlier addition of OA had better protective results, suggesting the early interact of OA with PA has played an important role in this scenario.

Conclusion

We found that PA could induce lipotoxicity on INS‐1E β‐cells. OA alone has no detrimental effects on β‐cells, and the combination of OA and PA has great potential to protect β‐cells against PA‐induced apoptosis. The interaction with PA and subsequent suppression of ER stress may contribute to the OA mediated protective effects on lipotoxicity in INS‐1E β‐cells.

Support or Funding Information

This study was supported by the Program of National Natural Science Foundation of China (31571474), and the National Key Clinical Project.