Activity of the acyl-CoA synthetase ACSL6 isoforms: role of the fatty acid Gate-domains

Soupène, Eric; Dinh, Nghi Phuong; Siliakus, Melvin; Kuypers, Frans A.

doi:10.1186/1471-2091-11-18

Cited by 47 publications

(43 citation statements)

References 27 publications

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“…We also found an apparently fixed and damaging variant of a PLTP orthologue, the protein product of which is involved in the synthesis and catabolism of high-density lipo-protein (38) and may affect the availability of triglycerides and weight gain during hyperphagia in PBs. In addition, we found fixed variants in two putative orthologues involved in longchain fatty acid synthesis and catabolism: CPT1B and ACSL6 (39,40). The fixed variants in these genes may be related to the fatty acid profile of PBs.…”

Section: Adaptation Of Pbs To Arctic Environment: Potential Signals Omentioning

confidence: 89%

Polar and brown bear genomes reveal ancient admixture and demographic footprints of past climate change

Miller

Schuster

Welch

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

328

375

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Polar bears (PBs) are superbly adapted to the extreme Arctic environment and have become emblematic of the threat to biodiversity from global climate change. Their divergence from the lower-latitude brown bear provides a textbook example of rapid evolution of distinct phenotypes. However, limited mitochondrial and nuclear DNA evidence conflicts in the timing of PB origin as well as placement of the species within versus sister to the brown bear lineage. We gathered extensive genomic sequence data from contemporary polar, brown, and American black bear samples, in addition to a 130,000-to 110,000-y old PB, to examine this problem from a genome-wide perspective. Nuclear DNA markers reflect a species tree consistent with expectation, showing polar and brown bears to be sister species. However, for the enigmatic brown bears native to Alaska's Alexander Archipelago, we estimate that not only their mitochondrial genome, but also 5-10% of their nuclear genome, is most closely related to PBs, indicating ancient admixture between the two species. Explicit admixture analyses are consistent with ancient splits among PBs, brown bears and black bears that were later followed by occasional admixture. We also provide paleodemographic estimates that suggest bear evolution has tracked key climate events, and that PB in particular experienced a prolonged and dramatic decline in its effective population size during the last ca. 500,000 years. We demonstrate that brown bears and PBs have had sufficiently independent evolutionary histories over the last 4-5 million years to leave imprints in the PB nuclear genome that likely are associated with ecological adaptation to the Arctic environment.demographic history | hybridization | mammalian genomics | phylogenetics G enome-scale studies of speciation and admixture have become essential tools in evolutionary analyses of recently diverged lineages. For example, paradigm-shifting genomic research on archaic and anatomically modern humans has identified critical gene flow events during hominin history (1, 2). However, aside from several analyses of domesticated species and their wild relatives (e.g., ref.3), studies that use whole-genome sequencing to investigate admixture in wildlife populations are only now beginning to emerge.The bear family (Ursidae, Mammalia) represents an excellent, largely untapped model for investigating complex speciation and rapid evolution of distinct phenotypes. Although polar bears (PBs; Ursus maritimus) and brown bears (Ursus arctos) are considered separate species, analyses of fossil evidence and mitochondrial sequence data have indicated a recent divergence of PBs from within brown bears (surveyed in ref. 4). For example, phylogenetic analyses of complete mitochondrial genomes, including from a unique 130,000-to 110,000-y-old PB jawbone from Svalbard, Norway, confirmed a particularly close relationship between PB and a genetically isolated population of brown bears from the Admiralty, Baranof, and Chichagof islands in Alaska's Alexander Archipelago (hereaf...

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Section: Adaptation Of Pbs To Arctic Environment: Potential Signals Omentioning

confidence: 89%

Polar and brown bear genomes reveal ancient admixture and demographic footprints of past climate change

Miller

Schuster

Welch

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

328

375

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“…Genes related to lipogenesis were significantly decreased in mice fed the HS diet, including those involved in fatty acid and lipid biosynthesis and transport (Scd2, Fabp5, Thrsp and Hmgcr) 20–23 , lipid endocytosis (Ldlr) 24 , and lipid esterification (Dgat2, Mogat2 and Plin2) 25–27 . Acsl6 is a negative regulator of lipid metabolism 28 . Conversely, genes related to lipolysis and fatty acid decomposition (specifically, Fabp3, Cpt1b, and Acot3) 29–31 , or carbohydrate utilization (Pck1 and Pdk4) 32, 33 were significantly up-regulated by the HS diet.…”

Section: Discussionmentioning

confidence: 99%

High-salt intake negatively regulates fat deposition in mouse

Cui

Yang

Zheng

et al. 2017

Sci Rep

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High-salt (HS) intake contributes to hypertension and cardiopathy, but the effect of HS on fat deposition is controversial. Feed intake, fat mass, the percentage of abdominal fat, heat production, rate of oxygen consumption and the respiratory exchange ratio of mice on a HS diet were significantly decreased (P < 0.01 or 0.05) compared with mice on a normal-salt (NS) diet. An in vitro experiment with differentiating pre-adipocytes showed reduced fat deposition in the presence of high concentrations of NaCl (>0.05 M). Abdominal fat mRNA profiles and protein measurements showed that 5 known genes involved in lipolysis were up-regulated significantly and 9 genes related to lipogenesis were down-regulated in HS mice. Abundant genes and some proteins (ATP2a1, AGT, and ANGPTL4) related to calcium ion metabolism or the renin-angiotensin system (RAS) were differentially expressed between HS and NS mice. Of special interest, CREB1 phosphorylation (S133 and S142), a key factor involved in calcium signaling and other pathways, was up-regulated in HS mice. By IPA analysis, a network mediated by calcium was established providing the molecular mechanisms underlying the negative effect of HS on fat deposition.

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“…These findings are supported by studies in rat brain, where it was observed to be involved in the incorporation of unsaturated fatty acids into phospholipids (Soupene et al . ; Chen et al . ).…”

Section: Discussionmentioning

confidence: 99%

Long‐chain acyl‐CoA synthetase 6 regulates lipid synthesis and mitochondrial oxidative capacity in human and rat skeletal muscle

Teodoro

Sampaio

Bomfim³

et al. 2016

The Journal of Physiology

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Long-chain acyl-CoA synthetases (ACSL 1 to 6) are key enzymes regulating the partitioning of acyl-CoA species toward different metabolic fates such as lipid synthesis or β-oxidation. Despite our understanding of ecotopic lipid accumulation in skeletal muscle being associated with metabolic diseases such as obesity and type II diabetes, the role of specific ACSL isoforms in lipid synthesis remains unclear. In the present study, we describe for the first time the presence of ACSL6 mRNA in human skeletal muscle and the role that ACSL6 plays in lipid synthesis in both rodent and human skeletal muscle. ACSL6 mRNA was observed to be up-regulated by acute high-fat meal ingestion in both rodents and humans. In rats, we also demonstrated that fasting and chronic aerobic training negatively modulated the ACSL6 mRNA and other genes of lipid synthesis. Similar results were obtained following ACSL6 knockdown in rat myotubes, which was associated with a decreased accumulation of TAGs and lipid droplets. Under the same knockdown condition, we further demonstrate an increase in fatty acid content, p-AMPK, mitochondrial content, mitochondrial respiratory rates and palmitate oxidation. These results were associated with increased PGC-1α, UCP2 and UCP3 mRNA and decreased reactive oxygen species production. In human myotubes, ACSL6 overexpression reduced palmitate oxidation and PGC-1α mRNA. In conclusion, ACSL6 drives acyl-CoA toward lipid synthesis and its downregulation improves mitochondrial biogenesis, respiratory capacity and lipid oxidation. These outcomes are associated with the activation of the AMPK/PGC1-α pathway.

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Activity of the acyl-CoA synthetase ACSL6 isoforms: role of the fatty acid Gate-domains

Cited by 47 publications

References 27 publications

Polar and brown bear genomes reveal ancient admixture and demographic footprints of past climate change

Polar and brown bear genomes reveal ancient admixture and demographic footprints of past climate change

High-salt intake negatively regulates fat deposition in mouse

Long‐chain acyl‐CoA synthetase 6 regulates lipid synthesis and mitochondrial oxidative capacity in human and rat skeletal muscle

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