Mechanisms involved in the cytotoxic and cytoprotective actions of saturated versus monounsaturated long-chain fatty acids in pancreatic beta-cells.
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.
Diakogiannaki
Eleftheria
E
Institute of Biomedical and Clinical Sciences, Peninsula Medical School, John Bull Building, Plymouth, Devon, UK.
Dhayal
Shalinee
S
Childs
Caroline E
CE
Calder
Philip C
PC
Welters
Hannah J
HJ
Morgan
Noel G
NG
D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D005227:Fatty Acids / Q000032:analysis / Q000378:metabolism / Q000494:pharmacology*; D005229:Fatty Acids, Monounsaturated / Q000378:metabolism / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism* / Q000473:pathology; D008856:Microscopy, Fluorescence; D010168:Palmitates / Q000494:pharmacology; D010743:Phospholipids / Q000737:chemistry / Q000378:metabolism; D051381:Rats; D014280:Triglycerides / Q000378:metabolism
D005227:Fatty Acids; D005229:Fatty Acids, Monounsaturated; D007328:Insulin; D010168:Palmitates; D010743:Phospholipids; D014280:Triglycerides; C008757:palmitoleic acid; C068012:methyl palmitoleate