Abstract
Dietary trans fatty acids (TFAs) have been implicated in serious health risks, yet little is known about their cellular effects and metabolism. We aim to undertake an in vitro comparison of two representative TFAs (elaidate and vaccenate) to the best-characterized endogenous cis-unsaturated FA (oleate). The present study addresses the possible protective action of TFAs on palmitate-treated RINm5F insulinoma cells with special regards to apoptosis, endoplasmic reticulum stress and the underlying ceramide and diglyceride (DG) accumulation. Both TFAs significantly improved cell viability and reduced apoptosis in palmitate-treated cells. They mildly attenuated palmitate-induced XBP-1 mRNA cleavage and phosphorylation of eukaryotic initiation factor 2α (eIF2α) and stress-activated protein kinase (SAPK)/c-Jun N-terminal kinase (JNK), but they were markedly less potent than oleate. Accordingly, all the three unsaturated FAs markedly reduced cellular palmitate incorporation and prevented harmful ceramide and DG accumulation. However, more elaidate or vaccenate than oleate was inserted into ceramides and DGs. Our results revealed a protective effect of TFAs in short-term palmitate toxicity, yet they also provide important in vitro evidence and even a potential mechanism for unfavorable long-term health effects of TFAs compared to oleate.
Highlights
The cell damage caused by sustained fatty acid (FA) oversupply is referred to as lipotoxicity, and it is known to play a central role in the development of certain obesity-related metabolic disorders, such as non-alcoholic fatty liver disease (NAFLD) [1,2], insulin resistance [3] and type 2 diabetes mellitus [4,5]
Lipotoxicity induced in pancreatic β-cells is of particular importance as it hinders the compensation of insulin resistance, which intensifies the primary damage through further increase in FA release from the adipocytes
It has been demonstrated that the enhancement of apoptosis and autophagy that leads to a reduction in β-cell mass is largely due to a destructive endoplasmic reticulum (ER) stress [7,9], which, in turn, is aggravated by the accumulation of toxic ceramide intermediates [10,11]
Summary
The cell damage caused by sustained fatty acid (FA) oversupply is referred to as lipotoxicity, and it is known to play a central role in the development of certain obesity-related metabolic disorders, such as non-alcoholic fatty liver disease (NAFLD) [1,2], insulin resistance [3] and type 2 diabetes mellitus [4,5]. Lipotoxicity induced in pancreatic β-cells is of particular importance as it hinders the compensation of insulin resistance, which intensifies the primary damage through further increase in FA release from the adipocytes. Severe malfunction of the ER leads to the activation of stress-activated protein kinase (SAPK)/c-Jun N-terminal kinase (JNK) and diverse caspase cascades, which contribute to β-cell apoptosis [12]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
