Regulation of human Δ-6 desaturase gene transcription: identification of a functional direct repeat-1 element

Tang, Chongren; Cho, Hyekung P.; Nakamura, Manabu; Clarke, Steven D.

doi:10.1194/jlr.m200195-jlr200

Cited by 131 publications

(57 citation statements)

References 42 publications

(78 reference statements)

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“…8, as well as with our prior proposal that this interaction may be enhanced by conformational changes in PC-TP that occur upon the binding of phosphatidylcholines with more unsaturated fatty acyl chains (10,12). In this connection, PPAR␣ activation promotes the synthesis of polyunsaturated fatty acids (38,39) and modulates the molecular species of phosphatidylcholines in the liver (40).…”

Section: Them2mentioning

confidence: 53%

“…Fasting promotes the interactions between Them2 and PC-TP. This could be attributable to PPAR␣-mediated enrichment of membranes with unsaturated phosphatidylcholines (38)(39)(40), which may induce conformational changes in PC-TP that favor binding to Them2 (12). (Top) As described previously (10), the Them2-PC-TP complex limits insulin signaling by decreasing IRS2 activation and stabilizing the TSC1-TSC2 complex, which suppresses mTOR.…”

Section: Fig 8 Schematic Model For Metabolic Regulation By Them2 and mentioning

confidence: 89%

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Thioesterase Superfamily Member 2 (Them2) and Phosphatidylcholine Transfer Protein (PC-TP) Interact To Promote Fatty Acid Oxidation and Control Glucose Utilization

Kawano

Ersoy

et al. 2014

Molecular and Cellular Biology

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Thioesterase superfamily member 2 (Them2) is a mitochondrion-associated long-chain fatty acyl coenzyme A (CoA) thioesterase that is highly expressed in the liver and oxidative tissues. Them2 activity in vitro is increased when it interacts with phosphatidylcholine transfer protein (PC-TP), a cytosolic lipid binding protein. Them2؊/؊ and Pctp ؊/؊ mice exhibit enhanced hepatic insulin sensitivity and increased adaptive thermogenesis, and Them2 ؊/؊ mice are also resistant to diet-induced hepatic steatosis. Although we showed previously that a Them2-PC-TP complex suppresses insulin signaling, the enzymatic activity of Them2 suggests additional direct involvement in regulating hepatic nutrient homeostasis. Here we used cultured primary hepatocytes to elucidate biochemical and cellular mechanisms by which Them2 and PC-TP regulate lipid and glucose metabolism. Under conditions simulating fasting, Them2 ؊/؊ and Pctp ؊/؊ hepatocytes each exhibited decreased rates of fatty acid oxidation and gluconeogenesis. In results indicative of Them2-dependent regulation by PC-TP, chemical inhibition of PC-TP failed to reproduce these changes in Them2 ؊/؊ hepatocytes. In contrast, rates of glucose oxidation and lipogenesis in the presence of high glucose concentrations were decreased only in Them2 ؊/؊ hepatocytes. These findings reveal a primary role for Them2 in promoting mitochondrial oxidation of fatty acids and glucose in the liver.

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Section: Them2mentioning

confidence: 53%

Section: Fig 8 Schematic Model For Metabolic Regulation By Them2 and mentioning

confidence: 89%

Thioesterase Superfamily Member 2 (Them2) and Phosphatidylcholine Transfer Protein (PC-TP) Interact To Promote Fatty Acid Oxidation and Control Glucose Utilization

Kawano

Ersoy

et al. 2014

Molecular and Cellular Biology

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“…In mice, PPAR α stimulates the conversion of malate into pyruvate to generate NADPH for lipogenesis by upregulating the expression of malic enzyme (ME1) [45]. Besides, the ∆5, ∆6, and ∆9 desaturases, rate-limiting enzymes in the synthesis of polyunsaturated FAs (PUFAs) from saturated FAs, are found in increased amounts after PPAR α activation [46–48]. The induction of desaturases could help to ensure that there are always enough PUFAs for their diverse functions, including being effective PPAR α agonists as proposed by others [46].…”

Section: Pparα In Livermentioning

confidence: 99%

The Role of PPARαActivation in Liver and Muscle

2010

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PPARα is one of three members of the soluble nuclear receptor family called peroxisome proliferator-activated receptor (PPAR). It is a sensor for changes in levels of fatty acids and their derivatives that responds to ligand binding with PPAR target gene transcription, inasmuch as it can influence physiological homeostasis, including lipid and carbohydrate metabolism in various tissues. In this paper we summarize the involvement of PPARα in the metabolically active tissues liver and skeletal muscle and provide an overview of the risks and benefits of ligand activation of PPARα, with particular consideration to interspecies differences.

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“…What ensues is a disturbed ratio of their substrates and products, in this case linoleic acid (LA, 18:2ω6) and dihomo-γ-linolenic acid (DGLA, 20:3ω6), respectively. The Δ 6 -catalyzed step required for conversion of 18:2ω6 to 20:3ω6 is usually the highest flux pathway [43], so an elevation in the 18:2ω6:20:3ω6 ratio may be a sensitive marker for zinc deficiency.…”

Section: Introductionmentioning

confidence: 99%

Dietary Zinc Deficiency Affects Blood Linoleic Acid: Dihomo-γ-linolenic Acid (LA:DGLA) Ratio; a Sensitive Physiological Marker of Zinc Status in Vivo (Gallus gallus)

et al. 2014

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Zinc is a vital micronutrient used for over 300 enzymatic reactions and multiple biochemical and structural processes in the body. To date, sensitive and specific biological markers of zinc status are still needed. The aim of this study was to evaluate Gallus gallus as an in vivo model in the context of assessing the sensitivity of a previously unexplored potential zinc biomarker, the erythrocyte linoleic acid: dihomo-γ-linolenic acid (LA:DGLA) ratio. Diets identical in composition were formulated and two groups of birds (n = 12) were randomly separated upon hatching into two diets, Zn(+) (zinc adequate control, 42.3 μg/g zinc), and Zn(−) (zinc deficient, 2.5 μg/g zinc). Dietary zinc intake, body weight, serum zinc, and the erythrocyte fatty acid profile were measured weekly. At the conclusion of the study, tissues were collected for gene expression analysis. Body weight, feed consumption, zinc intake, and serum zinc were higher in the Zn(+) control versus Zn(−) group (p < 0.05). Hepatic TNF-α, IL-1β, and IL-6 gene expression were higher in the Zn(+) control group (p < 0.05), and hepatic Δ6 desaturase was significantly higher in the Zn(+) group (p < 0.001). The LA:DGLA ratio was significantly elevated in the Zn(−) group compared to the Zn(+) group (22.6 ± 0.5 and 18.5 ± 0.5, % w/w, respectively, p < 0.001). This study suggests erythrocyte LA:DGLA is able to differentiate zinc status between zinc adequate and zinc deficient birds, and may be a sensitive biomarker to assess dietary zinc manipulation.

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Regulation of human Δ-6 desaturase gene transcription: identification of a functional direct repeat-1 element

Cited by 131 publications

References 42 publications

Thioesterase Superfamily Member 2 (Them2) and Phosphatidylcholine Transfer Protein (PC-TP) Interact To Promote Fatty Acid Oxidation and Control Glucose Utilization

Thioesterase Superfamily Member 2 (Them2) and Phosphatidylcholine Transfer Protein (PC-TP) Interact To Promote Fatty Acid Oxidation and Control Glucose Utilization

The Role of PPARαActivation in Liver and Muscle

Dietary Zinc Deficiency Affects Blood Linoleic Acid: Dihomo-γ-linolenic Acid (LA:DGLA) Ratio; a Sensitive Physiological Marker of Zinc Status in Vivo (Gallus gallus)

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