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Diabetes 54:2917-2924, 2005
© 2005 by the American Diabetes Association, Inc.
Increased Fatty Acid Desaturation and Enhanced Expression of Stearoyl Coenzyme A Desaturase Protects Pancreatic ß-Cells from Lipoapoptosis
1 Garvan Institute of Medical Research, St. Vincent’s Hospital, Sydney, Australia
2 Department of Biochemistry, University of Sydney, Sydney, Australia
Increased availability of fatty acids causes cell death and dysfunction in ß-cell lines, isolated islets, and animal models of diabetes. From the MIN6 ß-cell line, we selected two subpools that are resistant to palmitate-induced apoptosis. Protection was not universal because palmitate-resistant cells remained sensitive to cytokine- and streptozotocin-induced apoptosis. Palmitate oxidation and incorporation into cholesterol ester (but not triglycerides) were significantly higher in palmitate-resistant cells than in control cells. Consistent with these findings, transcript profiling revealed increased expression in palmitate-resistant cells of several ß-oxidation genes as well as a 2.8-fold upregulation of stearoyl-CoA desaturase 1 (SCD1). Correspondingly, the oleate-to-palmitate ratio of palmitate-resistant cells was double that of palmitate-pretreated control cells. At least some of this additional oleate in palmitate-resistant cells was incorporated into cholesterol ester stored in the form of large cytosolic lipid bodies. However, blocking cholesterol ester formation did not render palmitate-resistant cells sensitive to palmitate-induced apoptosis. On the other hand, an inhibitor of SCD1, 10,12-conjugated linoleic acid, dose dependently overcame the resistance of palmitate-resistant cells to lipoapoptosis. Our results suggest that desaturation per se is more important in protecting ß-cells from the cytotoxic effects of palmitate than is the nature of neutral lipid storage pool thus generated.
Address correspondence and reprint requests to Dr. Trevor Biden, Cell Signalling Group, Garvan Institute of Medical Research, 384 Victoria St., Darlinghurst, Sydney 2010, Australia. E-mail: t.biden{at}garvan.org.au
Abbreviations: ACAT, acyl-CoA:cholesterol acyltransferase; CLA, conjugated linoleic acid; CPT1, carnitine palmitoyl transferase 1; DMEM, Dulbecco’s modified Eagle’s medium; ROS, reactive oxygen species; SCD1, stearoyl-CoA desaturase 1; SPT1, serine palmitoyltransferase-1
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