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Mechanisms involved in the cytotoxic and cytoprotective actions of saturated versus monounsaturated long-chain fatty acids in pancreatic beta-cells.

Diakogiannaki E, Dhayal S, Childs CE, Calder PC, Welters HJ, Morgan NG - J. Endocrinol. (2007)

Bottom Line: 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.By contrast, methyl-palmitoleate failed to influence TAG levels (0.25 mM methyl-palmitoleate alone: 0.95 +/- 0.06 nmol TAG/10(6) cells; methyl-palmitoleate plus palmitate: 1.5 +/- 0.05) or its fatty acid composition in beta-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.

View Article: PubMed Central - PubMed

Affiliation: Institute of Biomedical and Clinical Sciences, Peninsula Medical School, John Bull Building, Plymouth, Devon, UK.

ABSTRACT
Long-chain saturated and monounsaturated fatty acids differ in their propensity to induce beta-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 beta-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 beta-cell phospholipid remodelling and increased TAG formation (control: 0.9 +/- 0.1 nmol TAG/10(6) 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/10(6) cells; methyl-palmitoleate plus palmitate: 1.5 +/- 0.05) or its fatty acid composition in beta-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.

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Mode of β-cell death following exposure to palmitate. BRIN-BD11 cells were treated for 18 h in the absence (control) or presence of 0·1 mM palmitate. The numbers of live (white bars), apoptotic (solid grey bars) and necrotic (cross-hatched bars) cells were estimated by fluorescence microscopy after staining with propidium iodide and Hoechst 33342. *Significantly reduced (P<0·001) when compared with vehicle-treated cells; **significantly increased (P<0·001) when compared with vehicle-treated cells.
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fig1: Mode of β-cell death following exposure to palmitate. BRIN-BD11 cells were treated for 18 h in the absence (control) or presence of 0·1 mM palmitate. The numbers of live (white bars), apoptotic (solid grey bars) and necrotic (cross-hatched bars) cells were estimated by fluorescence microscopy after staining with propidium iodide and Hoechst 33342. *Significantly reduced (P<0·001) when compared with vehicle-treated cells; **significantly increased (P<0·001) when compared with vehicle-treated cells.

Mentions: In confirmation of previous observations (Welters et al. 2004, 2006), incubation of BRIN-BD11 cells with palmitate dose-dependently reduced their viability as judged by either trypan blue exclusion or staining with propidium iodide/Hoechst 33342. This effect was primarily due to increased apoptosis as judged by fluorescence microscopy after staining with propidium iodide and Hoechst 33342 (Fig. 1). By contrast, palmitoleate was not toxic to the cells at concentrations up to 0.25 mM. Cells exposed to both palmitate and palmitoleate simultaneously also retained viability (0·25 mM palmitate alone: 89±8% non-viable cells; 0·25 mM palmitoleate alone: 9±3% non-viable cells; palmitate plus palmitoleate: 19±3% non-viable cells (P<0·001 versus palmitate alone)), suggesting that palmitoleate was actively protective against palmitate-induced cytotoxicity.


Mechanisms involved in the cytotoxic and cytoprotective actions of saturated versus monounsaturated long-chain fatty acids in pancreatic beta-cells.

Diakogiannaki E, Dhayal S, Childs CE, Calder PC, Welters HJ, Morgan NG - J. Endocrinol. (2007)

Mode of β-cell death following exposure to palmitate. BRIN-BD11 cells were treated for 18 h in the absence (control) or presence of 0·1 mM palmitate. The numbers of live (white bars), apoptotic (solid grey bars) and necrotic (cross-hatched bars) cells were estimated by fluorescence microscopy after staining with propidium iodide and Hoechst 33342. *Significantly reduced (P<0·001) when compared with vehicle-treated cells; **significantly increased (P<0·001) when compared with vehicle-treated cells.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC1994570&req=5

fig1: Mode of β-cell death following exposure to palmitate. BRIN-BD11 cells were treated for 18 h in the absence (control) or presence of 0·1 mM palmitate. The numbers of live (white bars), apoptotic (solid grey bars) and necrotic (cross-hatched bars) cells were estimated by fluorescence microscopy after staining with propidium iodide and Hoechst 33342. *Significantly reduced (P<0·001) when compared with vehicle-treated cells; **significantly increased (P<0·001) when compared with vehicle-treated cells.
Mentions: In confirmation of previous observations (Welters et al. 2004, 2006), incubation of BRIN-BD11 cells with palmitate dose-dependently reduced their viability as judged by either trypan blue exclusion or staining with propidium iodide/Hoechst 33342. This effect was primarily due to increased apoptosis as judged by fluorescence microscopy after staining with propidium iodide and Hoechst 33342 (Fig. 1). By contrast, palmitoleate was not toxic to the cells at concentrations up to 0.25 mM. Cells exposed to both palmitate and palmitoleate simultaneously also retained viability (0·25 mM palmitate alone: 89±8% non-viable cells; 0·25 mM palmitoleate alone: 9±3% non-viable cells; palmitate plus palmitoleate: 19±3% non-viable cells (P<0·001 versus palmitate alone)), suggesting that palmitoleate was actively protective against palmitate-induced cytotoxicity.

Bottom Line: 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.By contrast, methyl-palmitoleate failed to influence TAG levels (0.25 mM methyl-palmitoleate alone: 0.95 +/- 0.06 nmol TAG/10(6) cells; methyl-palmitoleate plus palmitate: 1.5 +/- 0.05) or its fatty acid composition in beta-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.

View Article: PubMed Central - PubMed

Affiliation: Institute of Biomedical and Clinical Sciences, Peninsula Medical School, John Bull Building, Plymouth, Devon, UK.

ABSTRACT
Long-chain saturated and monounsaturated fatty acids differ in their propensity to induce beta-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 beta-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 beta-cell phospholipid remodelling and increased TAG formation (control: 0.9 +/- 0.1 nmol TAG/10(6) 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/10(6) cells; methyl-palmitoleate plus palmitate: 1.5 +/- 0.05) or its fatty acid composition in beta-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.

Show MeSH
Related in: MedlinePlus