Modulation of palmitate-induced endoplasmic reticulum stress and apoptosis in pancreatic β-cells by stearoyl-CoA desaturase and Elovl6

Green, Christopher D.; Olson, L. Karl

doi:10.1152/ajpendo.00544.2010

Cited by 106 publications

(88 citation statements)

References 75 publications

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“…Furthermore, LA-4 cells treated with siElovl6 showed an increase in both C16 PA and palmitoleic acid, and a decrease in both C18 stearic acid and OA. These findings were consistent with previous reports describing the effects of Elovl6 deficiency on hepatocytes and pancreatic b-cells 15,16,24 . Of particular interest, we note that C18:2n-6 (LA), an essential PUFA that can only be synthesized from dietary precursors, was decreased in Elovl6 À / À lung compared with those in WT lung.…”

Section: Blm Treatment Decreases Elovl6 Expression In the Lungsupporting

confidence: 93%

Deranged fatty acid composition causes pulmonary fibrosis in Elovl6-deficient mice

et al. 2013

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Despite the established role of alveolar type II epithelial cells for the maintenance of pulmonary function, little is known about the deregulation of lipid composition in the pathogenesis of pulmonary fibrosis. The elongation of long-chain fatty acids family member 6 (Elovl6) is a rate-limiting enzyme catalysing the elongation of saturated and monounsaturated fatty acids. Here we show that Elovl6 expression is significantly downregulated after an intratracheal instillation of bleomycin (BLM) and in human lung with idiopathic pulmonary fibrosis. Elovl6-deficient (Elovl6 À / À ) mice treated with BLM exhibit severe fibroproliferative response and derangement of fatty acid profile compared with wild-type mice. Furthermore, Elovl6 knockdown induces a change in fatty acid composition similar to that in Elovl6 À / À mice, resulting in induction of apoptosis, TGF-b1 expression and reactive oxygen species generation. Our findings demonstrate a previously unappreciated role for Elovl6 in the regulation of lung homeostasis, and in pathogenesis and exacerbation of BLM-induced pulmonary fibrosis.

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Section: Blm Treatment Decreases Elovl6 Expression In the Lungsupporting

confidence: 93%

Deranged fatty acid composition causes pulmonary fibrosis in Elovl6-deficient mice

et al. 2013

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“…Scd1 expression is associated with the regulation of survival and proliferation signals in normal and cancer cells. Decrease in scd1 expression triggered either apoptosis in cancer cells or increase in palmitate-induced cytotoxicity in endothelial and pancreatic beta cells (Green and Olson 2011;Minville-Walz et al 2010;Peter et al 2008). We demonstrated here that the down-regulation of stearoylCoA desaturase expression and activity with oleic acid (OA) or trans-11 vaccenic acid (VA) treatment did not affect viability of HASMC.…”

Section: Discussionmentioning

confidence: 81%

Distinct regulation of stearoyl-CoA desaturase 1 gene expression by cis and trans C18:1 fatty acids in human aortic smooth muscle cells

et al. 2011

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Consumption of trans fatty acids is positively correlated with cardiovascular diseases and with atherogenic risk factors. Trans fatty acids might play their atherogenic effects through lipid metabolism alteration of vascular cells. Accumulation of lipids in vascular smooth muscle cells is a feature of atherosclerosis and a consequence of lipid metabolism alteration. Stearoyl-CoA desaturase 1 (scd1) catalyses the production of monounsaturated fatty acids (e.g. oleic acid) and its expression is associated with lipogenesis induction and with atherosclerosis development. We were interested in analysing the regulation of delta-9 desaturation rate and scd1 expression in human aortic smooth muscle cells (HASMC) exposed to cis and trans C18:1 fatty acid isomers (cis-9 oleic acid, trans-11 vaccenic acid or trans-9 elaidic acid) for 48 h at 100 lM. Treatment of HASMC with these C18:1 fatty acid isomers led to differential effects on delta-9 desaturation; oleic acid repressed the desaturation rate more potently than trans-11 vaccenic acid, whereas trans-9 elaidic acid increased the delta-9 desaturation rate. We then correlated the delta-9 desaturation rate with the expression of scd1 protein and mRNA. We showed that C18:1 fatty acids controlled the expression of scd1 at the transcriptional level in HASMC, leading to an increase in scd1 mRNA content by trans-9 elaidic acid treatment, whereas a decrease in scd1 mRNA content was observed with cis-9 oleic acid and trans-11 vaccenic acid treatments. Altogether, this work highlights a differential capability of C18:1 fatty acid isomers to control scd1 gene expression, which presumes of different consequent effects on cell functions.

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“…It is not excluded that the increase of lipogenic enzyme gene expressions in white adipose tissue may be part of the molecular mechanism(s) by which the increase of fatty acid synthesis after food restriction/refeeding confers enhanced susceptibility to obesity and insulin resistance. However, one has to keep in mind that up-regulation of Scd1 and the knockdown of Elovl6 is beneficial for pancreatic beta cells by protecting them from saturated fatty acid-induced ER stress and apoptosis [28].…”

Section: Discussionmentioning

confidence: 99%

Unusual increase of Scd1 and Elovl6 expression in rat inguinal adipose tissue

et al. 2012

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It is generally accepted that the location of body fat deposits may play an important role in the risk of developing some endocrine and metabolic diseases. We have studied the effect of food restriction and food restriction/refeeding, often practiced by individuals trying to lose body weight, on the expression of genes which are associated with obesity and certain metabolic disorders in inguinal, epididymal, and perirenal rat white adipose tissues. Gene expression was analyzed by real time semi-quantitative polymerase chain reaction and by Western blot. We found that prolonged food restriction caused a significant decrease of body and adipose tissue mass as well as the increase of Scd1 and Elovl6 gene expressions in all main rat adipose tissue deposits. Food restriction/refeeding caused increases of: a) Scd1 and Elovl6 mRNA levels in adipose tissue, b) Scd1 protein level and c) desaturation index in adipose tissue. The increased expression of both genes was unusually high in inguinal adipose tissue. The results suggest that the increase of Scd1 and Elovl6 gene expressions in white adipose tissue by prolonged food restriction and prolonged food restriction/refeeding may contribute to accelerated fat recovery that often occurs in individuals after food restriction/refeeding.

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Modulation of palmitate-induced endoplasmic reticulum stress and apoptosis in pancreatic β-cells by stearoyl-CoA desaturase and Elovl6

Cited by 106 publications

References 75 publications

Deranged fatty acid composition causes pulmonary fibrosis in Elovl6-deficient mice

Deranged fatty acid composition causes pulmonary fibrosis in Elovl6-deficient mice

Distinct regulation of stearoyl-CoA desaturase 1 gene expression by cis and trans C18:1 fatty acids in human aortic smooth muscle cells

Unusual increase of Scd1 and Elovl6 expression in rat inguinal adipose tissue

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