Structure-toxicity relationships of saturated and unsaturated free fatty acids for elucidating the lipotoxic effects in human EndoC-βH1 beta-cells

Plötz, Thomas; Hanstein, A.; Krümmel, B; Laporte, Anna; Mehmeti, Ilir; Lenzen, Sigurd

doi:10.1016/j.bbadis.2019.08.001

Cited by 44 publications

(112 citation statements)

References 41 publications

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“…EndoC-βH1 beta-cells (passages 3-30) and isolated rat islets (from 6 male Lewis rats of 300-400 g) were incubated with different FFA compositions for 24 or 48 h. Thereafter caspase-3 activity 12 and for EndoC-βH1 beta-cells lipid droplet formation 13 , H 2 O 2 generation (see Supplementary Information), as well as RT-PCR for the quantification of ER-stress marker 12 , were measured as described.…”

Section: Experimental Methodsmentioning

confidence: 99%

Toxicity of fatty acid profiles of popular edible oils in human EndoC-βH1 beta-cells

2020

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An inappropriate diet, particularly excessive consumption of dietary fats and oils, may have a major negative impact on beta-cell function and cause type 2 diabetes mellitus. To investigate this issue, we examined the toxicity of free fatty acid (FFA) compositions mirroring the FFA profiles of various popular edible oils in human EndoC-βH1 beta-cells and in rat islets. For this purpose, we made compositions consisting exclusively of various FFAs in different volumetric percentages mimicking these oils and additionally mixtures of these compositions. Human EndoC-βH1 beta-cells were incubated with different oil compositions and the toxicity, lipid droplet formation, ER-stress, and H 2 O 2 production were analyzed. Compositions with prominent content of saturated as well as unsaturated long-chain FFAs showed moderate but significant toxicity both in human EndoC-βH1 beta-cells and rat islets, however, without further measurable metabolic impairments. On the other hand compositions with high content of medium-chain FFAs revealed no toxicity. A composition with 50% of the very long-chain unsaturated FFA erucic acid caused high toxicity with concomitant peroxisomal H 2 O 2 production. The toxicity of FFAs to human EndoC-βH1 beta-cells was dampened in mixtures of FFA compositions with a significant content of medium-chain FFAs, but not with a significant proportion of unsaturated FFAs.

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Section: Experimental Methodsmentioning

confidence: 99%

Toxicity of fatty acid profiles of popular edible oils in human EndoC-βH1 beta-cells

2020

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“…The ndings of this study support those of earlier reports [26][27][28] in which EndoC-βH1 cells were shown to be resistant to C16:0 at concentrations of up to 1 mM during exposure periods of 72 h, both in the absence and presence of high glucose concentrations. However, they are at odds with the work of Plötz et al who reported that C16:0, C18:0, C19:0 and C18:1 were toxic to EndoC-βH1 cells [10,29]. Currently, we are uncertain of the reasons for this disparity but it may re ect technical differences since the studies of Plötz et al mainly used caspase 3 activity measurement as a surrogate for apoptosis although they also compared these with other measures of toxicity.…”

Section: Discussionmentioning

confidence: 95%

Long-chain Saturated Fatty Acid Species Are Not Toxic to Human Pancreatic Β-cells and May Offer Protection Against Pro-inflammatory Cytokine Induced β-cell Death

Thomas

Kaiyven

Welters

et al. 2020

Preprint

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Obesity is a major risk factor for type 2 diabetes (T2D) although the causal links remain unclear. A feature shared by both conditions however is systemic inflammation and raised levels of circulating fatty acids (FFA). It is widely believed that in obese individuals genetically prone to T2D, elevated levels of plasma FFA may contribute towards the death and dysfunction of insulin-producing pancreatic β-cells in a process of (gluco)lipotoxicity. In support of this, in vitro studies have shown consistently that long-chain saturated fatty acids (LC-SFA) are toxic to rodent β-cells during chronic exposure (>24h). Conversely, shorter chain SFA and unsaturated species are well tolerated, suggesting that toxicity is dependent on carbon chain length and/or double bond configuration. Despite the wealth of evidence implicating lipotoxicity as a means of β-cell death in rodents, the evidence that a similar process occurs in humans is much less substantial. Therefore, the present study has evaluated the effects of chronic exposure to fatty acids of varying chain length and degree of saturation, on the viability of human β-cells in culture. We have also studied the effects of a combination of fatty acids and pro-inflammatory cytokines. Strikingly, we find that LC-FFA do not readily promote the demise of human β-cells and that they may even offer a measure of protection against the toxic effects of pro-inflammatory cytokines. Therefore, these findings imply that a model in which elevated circulating LC-FFA play a direct role in mediating β-cell dysfunction and death in humans, may be overly simplistic.

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“…Because the individual fatty acid differently affects its biological activity (Plötz et al, ), we determined the fatty acid compositions of duck and lard oils. As shown in Table , the difference in the fatty acid composition was observed in duck and lard oils.…”

Section: Resultsmentioning

confidence: 99%

“…However, the molecular mechanism(s) underlying the DO‐NE‐mediated attenuation of lipotoxicity remains unclear. A partial explanation for this event is that high ratio of double bonds of duck oil retards the metabolic flux rate and hampers the production of hydrogen peroxide in the β‐oxidation pathways leading to the reduction in hepatic injury (Plötz et al, ). DO‐NE may therefore exert its action on the lipotoxicity through blockade of ROS, which are cellular signaling molecules that regulate gene expression such as PPAR‐γ and SREBP‐1 that directly associated with hepatic lipid accumulation (Eeckhoute et al, ; Ruiz et al, ).…”

Section: Resultsmentioning

confidence: 99%

Comparative effects of nanoemulsions loaded with duck oil and lard oil on palmitate‐induced lipotoxicity

Kang

Hur

et al. 2019

J Food Biochem

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The effects of duck oil and lard oil on lipotoxicity induced by saturated long‐chain fatty acids were evaluated in HepG2 cells. Lipotoxicity triggered by palmitate, a saturated fatty acid, was inhibited more by duck oil‐loaded nanoemulsion (DO‐NE) than by lard oil‐loaded nanoemulsion (LO‐NE) and control nanoemulsion (NE) in HepG2 cells. Accumulation of reactive oxygen species and lipid vacuoles in HepG2 cells induced by palmitate treatment was inhibited by DO‐NE but not by LO‐NE. Consistently, treatment of HepG2 cells with DO‐NE, but not with NE or LO‐NE, significantly reduced the expression levels of peroxisome proliferator‐activated receptor‐γ2 and sterol regulatory element‐binding protein‐1, which are key regulatory proteins in hepatic lipid accumulation. In addition, the cleavage of poly (ADP‐ribose) polymerase and caspase‐3 were reduced more by DO‐NE than by LO‐NE, indicating that DO‐NE directly attenuates cellular damage induced by palmitate. Collectively, these results imply that the biological activity of duck oil against palmitate‐induced cellular damage is more potent than that of lard oil. Practical applications Accumulated lipids in nonadipose tissues, especially the liver, cause lipotoxicity, a pathologic feature of hepatic disorders, by inducing oxidative stress. A nanoemulsion loaded with duck oil, which is a functional food widely consumed by Korean people, inhibited lipotoxicity by suppressing lipid accumulation in HepG2 cells exposed to palmitate, which mimic nonalcoholic fatty liver disease. Thus, we propose that duck oil can be used as a functional food to improve lipid‐induced hepatic disorders.

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Structure-toxicity relationships of saturated and unsaturated free fatty acids for elucidating the lipotoxic effects in human EndoC-βH1 beta-cells

Cited by 44 publications

References 41 publications

Toxicity of fatty acid profiles of popular edible oils in human EndoC-βH1 beta-cells

Toxicity of fatty acid profiles of popular edible oils in human EndoC-βH1 beta-cells

Long-chain Saturated Fatty Acid Species Are Not Toxic to Human Pancreatic Β-cells and May Offer Protection Against Pro-inflammatory Cytokine Induced β-cell Death

Comparative effects of nanoemulsions loaded with duck oil and lard oil on palmitate‐induced lipotoxicity

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