Role of fatty acid elongases in determination of de novo synthesized monounsaturated fatty acid species

Green, Christopher D.; Ozguden-Akkoc, Cansel G.; Wang, Yun; Jump, Donald Β.; Olson, L. Karl

doi:10.1194/jlr.m004747

Cited by 141 publications

(153 citation statements)

References 28 publications

(60 reference statements)

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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: 83%

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: 83%

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

et al. 2013

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“…This is also consistent with the results of Grunnet et al (Rangan and Smith, 1996). An alternative hypothesis is that inhibited FASN increased malonyl-CoA content which was reported to inhibit the increasing of C10:0 fatty acid content induced by extra albumin (Green et al, 2010). Although decreased ACCα may partly alleviate the increasing trend of malonyl-CoA, it is just through as a feedback regulation to alleviate the effect of FASN reducing.…”

Section: Discussionmentioning

confidence: 96%

“…The predominant product of FASN is a 16-carbon long-chain palmitate in non-ruminants. Palmitate is a significant material for triglyceride synthesis and fatty acid elongation, which is believed to be the main source of mono-unsaturated fatty acids in rat insulinoma cell line (Green et al, 2010). However, FASN can also produce smaller amounts of myristate, laureate, and even shorter-chain fatty acids in lactation mammary gland (Hillgartner et al, 1995) and rat liver (Hansen et al, 1970).…”

Section: Introductionmentioning

confidence: 99%

Inhibition of FASN reduces the synthesis of medium-chain fatty acids in goat mammary gland

Zhu

Luo

Wang

et al. 2014

Animal

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Fatty acid synthase (FASN) is known as a crucial enzyme of cellular de novo fatty acid synthesis in mammary gland which has been proved as the main source of short and medium-chain fatty acids of milk. However, the regulatory role of FASN in goat-specific milk fatty acids composition remains unclear. We cloned and analyzed the full-length of FASN gene from the mammary gland of Capra hircus (Xinong Saanen dairy goat) (DQ 915966). Comparative gene expression analysis suggested that FASN is predominantly expressed in fat, small intestine and mammary gland tissues, and expresses higher level at lactation period. Inhibition of FASN activity by different concentrations (0, 5, 15, 25 and 35 μM) of orlistat, a natural inhibitor of FASN, resulted in decreased expression of acetyl-CoA carboxylase α (ACCα), lipoprotein lipase and heart-type fatty acid binding protein (H-FABP) in a concentration-dependent manner in goat mammary gland epithelial cells (GMEC). Similar results were also obtained by silencing of FASN. Additionally, reduction of FASN expression also led to apparent decline of the relative content of decanoic acid (C10:0) and lauric acid (C12:0) in GMEC. Our study provides a direct evidence for inhibition of FASN reduces cellular medium-chain fatty acids synthesis in GMEC.

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“…It is interesting to note that a different response to diet is observed for ELOVL5 and ELOVL6 genes, in spite of having a similar role. Their different behavior may be due to different substrate specificity and availability, as ELOVL5 preferentially elongates PUFA, while ELOVL6 more effectively elongates SFA and MUFA (Jakobsson et al, 2006;Green et al, 2010). The higher availability of SFA and MUFA synthetized from dietary CH, which is observed at the tissue composition level (Óvilo et al, 2014), would particularly induce the ELOVL6 expression.…”

Section: Discussionmentioning

confidence: 99%

Adipose tissue transcriptional response of lipid metabolism genes in growing Iberian pigs fed oleic acid v. carbohydrate enriched diets

Benítez¹,

Núñez²,

Fernández³

et al. 2016

Animal

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Diet influences animal body and tissue composition due to direct deposition and to the nutrients effects on metabolism. The influence of specific nutrients on the molecular regulation of lipogenesis is not well characterized and is known to be influenced by many factors including timing and physiological status. A trial was performed to study the effects of different dietary energy sources on lipogenic genes transcription in ham adipose tissue of Iberian pigs, at different growth periods and on feeding/fasting situations. A total of 27 Iberian male pigs of 28 kg BW were allocated to two separate groups and fed with different isocaloric feeding regimens: standard diet with carbohydrates as energy source (CH) or diet enriched with high oleic sunflower oil (HO). Ham subcutaneous adipose tissue was sampled by biopsy at growing (44 kg mean BW) and finishing (100 kg mean BW) periods. The first sampling was performed on fasted animals, while the last sampling was performed twice, with animals fasted overnight and 3 h after refeeding. Effects of diet, growth period and feeding/fasting status on gene expression were explored quantifying the expression of a panel of key genes implicated in lipogenesis and lipid metabolism processes. Quantitative PCR revealed several differentially expressed genes according to diet, with similar results at both timings: RXRG, LEP and FABP5 genes were upregulated in HO group while ME1, FASN, ACACA and ELOVL6 were upregulated in CH. The diet effect on ME1 gene expression was conditional on feeding/fasting status, with the higher ME1 gene expression in CH than HO groups, observed only in fasting samples. Results are compatible with a higher de novo endogenous synthesis of fatty acids (FA) in the carbohydrate-supplemented group and a higher FA transport in the oleic acid-supplemented group. Growth period significantly affected the expression of most of the studied genes, with all but PPARG showing higher expression in finishing pigs according to a pattern dissimilar from the usual in cosmopolitan pig breeds. Feeding/fasting status only influenced PPARG gene transcription. The lack of effects of feeding/ fasting status on lipogenic gene expression and the higher ME1 response to diet in fasting samples than in postprandial sampling, suggest the persistence of de novo lipogenesis during fasting. Overall results improve the understanding of the influence of different factors on lipid metabolism regulation in Iberian pigs.

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Role of fatty acid elongases in determination of de novo synthesized monounsaturated fatty acid species

Cited by 141 publications

References 28 publications

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

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

Inhibition of FASN reduces the synthesis of medium-chain fatty acids in goat mammary gland

Adipose tissue transcriptional response of lipid metabolism genes in growing Iberian pigs fed oleic acid v. carbohydrate enriched diets

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