scholarly journals Mechanisms involved in the cytotoxic and cytoprotective actions of saturated versus monounsaturated long-chain fatty acids in pancreatic β-cells

2007 ◽  
Vol 194 (2) ◽  
pp. 283-291 ◽  
Author(s):  
Eleftheria Diakogiannaki ◽  
Shalinee Dhayal ◽  
Caroline E Childs ◽  
Philip C Calder ◽  
Hannah J Welters ◽  
...  

Long-chain saturated and monounsaturated fatty acids differ in their propensity to induce β-cell death in vitro with palmitate (C16:0) being cytotoxic, whereas palmitoleate (C16:1n-7) is cytoprotective. We now show that this cytoprotective capacity extends to a poorly metabolised C16:1n-7 derivative, methyl-palmitoleate (0.25 mM palmitate alone: 92 ± 4% death after 18 h; palmitate plus 0.25 mM methyl-palmitoleate: 12 ± 2%; P < 0.001). Palmitoleate and its methylated derivative also acted as mitogens in cultured β-cells (5-bromo-2-deoxyuridine incorporation – control: 0.15 ± 0.01 units; 0.25 mM palmitoleate: 0.22 ± 0.01 units; P < 0.05). It has been proposed that alterations in neutral lipid synthesis (particularly triacylglycerol (TAG) formation) might mediate the differential responses to saturated and unsaturated fatty acids and we have examined this proposition. Palmitate and palmitoleate both promoted β-cell phospholipid remodelling and increased TAG formation (control: 0.9 ± 0.1 nmol TAG/106 cells; 0.25 mM palmitate: 1.55 ± 0.07; 0.25 mM palmitoleate: 1.4 ± 0.05; palmitate plus palmitoleate: 2.3 ± 0.1). By contrast, methyl-palmitoleate failed to influence TAG levels (0.25 mM methyl-palmitoleate alone: 0.95 ± 0.06 nmol TAG/106 cells; methyl-palmitoleate plus palmitate: 1.5 ± 0.05) or its fatty acid composition in β-cells exposed to palmitate. The results suggest that monounsaturated fatty acids can promote cell viability and mitogenesis by a mechanism that does not require their metabolism and is independent of alterations in TAG formation.

2008 ◽  
Vol 36 (5) ◽  
pp. 905-908 ◽  
Author(s):  
Noel G. Morgan ◽  
Shalinee Dhayal ◽  
Eleftheria Diakogiannaki ◽  
Hannah J. Welters

Chronic exposure of pancreatic β-cells to long-chain fatty acids can cause loss of secretory function and enhanced apoptosis by a process of ‘lipotoxicity’, which may be a contributory factor to the rising incidence of Type 2 diabetes in humans. However, when incubated in vitro, β-cells respond differentially to long-chain saturated and mono-unsaturated fatty acids, suggesting that these molecules may regulate cell functionality by different mechanisms. In particular, it is clear that, whereas saturated fatty acids [e.g. palmitate (C16:0)] exert detrimental effects on β-cells, the equivalent mono-unsaturated species [e.g. palmitoleate (C16:1)] are well tolerated. Indeed, mono-unsaturated species are potently cytoprotective. The present review explores the differential effects of these various fatty acids on β-cell viability and considers the possible mechanisms involved in cytoprotection by mono-unsaturates.


2008 ◽  
Vol 36 (5) ◽  
pp. 959-962 ◽  
Author(s):  
Eleftheria Diakogiannaki ◽  
Noel G. Morgan

Recent evidence indicates that treatment of pancreatic β-cells with long chain fatty acids can lead to the development of an ER (endoplasmic reticulum) stress response. This is manifest as the activation of some components of the PERK [RNA-dependent protein kinase-like ER eIF2α (eukaryotic initiation factor 2α) kinase]-dependent arm of ER stress and is seen most dramatically when cells are treated with long-chain saturated fatty acids (e.g. palmitate). By contrast, the equivalent mono-unsaturates (e.g. palmitoleate) are much less effective and they can even attenuate the ER stress response to palmitate. This may be due to the regulation of eIF2α phosphorylation in cells exposed to mono-unsaturates. The present review discusses the differential effects of saturated and mono-unsaturated fatty acids on ER stress in β-cells and considers the extent to which regulation of this pathway may be involved in mediating their effects on viability.


1984 ◽  
Vol 67 (7) ◽  
pp. 1439-1444 ◽  
Author(s):  
William Chalupa ◽  
Bonnie Rickabaugh ◽  
D. Kronfeld ◽  
S. David Sklan

2006 ◽  
Vol 5 (12) ◽  
pp. 2047-2061 ◽  
Author(s):  
Jana Klose ◽  
James W. Kronstad

ABSTRACT The transition from yeast-like to filamentous growth in the biotrophic fungal phytopathogen Ustilago maydis is a crucial event for pathogenesis. Previously, we showed that fatty acids induce filamentation in U. maydis and that the resulting hyphal cells resemble the infectious filaments observed in planta. To explore the potential metabolic role of lipids in the morphological transition and in pathogenic development in host tissue, we deleted the mfe2 gene encoding the multifunctional enzyme that catalyzes the second and third reactions in β-oxidation of fatty acids in peroxisomes. The growth of the strains defective in mfe2 was attenuated on long-chain fatty acids and abolished on very-long-chain fatty acids. The mfe2 gene was not generally required for the production of filaments during mating in vitro, but loss of the gene blocked extensive proliferation of fungal filaments in planta. Consistent with this observation, mfe2 mutants exhibited significantly reduced virulence in that only 27% of infected seedlings produced tumors compared to 88% tumor production upon infection by wild-type strains. Similarly, a defect in virulence was observed in developing ears upon infection of mature maize plants. Specifically, the absence of the mfe2 gene delayed the development of teliospores within mature tumor tissue. Overall, these results indicate that the ability to utilize host lipids contributes to the pathogenic development of U. maydis.


1992 ◽  
Vol 157 (3) ◽  
pp. 223-228 ◽  
Author(s):  
Naoki Morita ◽  
Nobuhiro Okajima ◽  
Masaru Gotoh ◽  
Hideyuki Hayashi ◽  
Hidetoshi Okuyama ◽  
...  

1969 ◽  
Vol 36 (2) ◽  
pp. 169-175 ◽  
Author(s):  
Sonja Mattsson ◽  
P. Swartling ◽  
R. Nilsson

SummarySummer and winter milk-fat samples from 14 dairies in Sweden were fractionated by crystallization from acetone solution (1:8) at 15 °C. The composition of the major fatty acids of the parent milk fat and of the acetone insoluble fraction were examined by GLC, and the gross triglyceride pattern by TLC on plates of silicic acid treated with silver nitrate.The fatty acid composition of the milk fat was similar to that of milk fat from other countries and varied according to season and also, to a smaller extent, from region to region. Four fractions, representing 33–45, 41–34, 18–14 and 7–6 % of the fat and which contained progressively smaller proportions of saturated acids, were obtained by TLC.The acetone insoluble glyceride (AIG) fraction was characterized by a smaller content of short-chain fatty acids and unsaturated fatty acids, and a larger content of saturated long-chain fatty acids, than the parent milk fat. AIGs from summer milk fat contained a larger proportion of C18 acids and a smaller proportion of C6–C16 acids than AIGs from winter milk fat.Four fractions representing 62–70, 15–8, 16–15 and 7 % of the AIG fraction were obtained by TLC. The distribution of the triglycerides in the AIG fraction differed from that in the parent milk fat, mostly in the relative amounts of glycerides in the 2 most saturated TLC fractions. The seasonal variation was largely confined to these 2 fractions.


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