A lipidomic screen of palmitate-treated MIN6 beta-cells links sphingolipid metabolites with endoplasmic reticulum (ER) stress and impaired protein trafficking (vol 435, pg 267, 2011)
E Boslem, G MacIntosh, AM Preston, C Bartley, AK Busch, M Fuller, DR Laybutt, PJ Meikle, TJ Biden
BIOCHEMICAL JOURNAL | PORTLAND PRESS LTD | Published : 2011
Saturated fatty acids promote lipotoxic ER (endoplasmic reticulum) stress in pancreatic β-cells in association with Type 2 diabetes. To address the underlying mechanisms we employed MS in a comprehensive lipidomic screen of MIN6 β-cells treated for 48 h with palmitate. Both the overall mass and the degree of saturation of major neutral lipids and phospholipids were only modestly increased by palmitate. The mass of GlcCer (glucosylceramide) was augmented by 70% under these conditions, without any significant alteration in the amounts of either ceramide or sphingomyelin. However, flux into ceramide (measured by [3H]serine incorporation) was augmented by chronic palmitate, and inhibition of cer..View full abstract
This work was supported by the National Heath and Medical Research Council of Australia project grant (to T.J.B. and D.R.L.), Research Fellowships (to T.J.B. and P.J.M.), and a postgraduate scholarship (to E.B.).