Glucocorticoid and mineralocorticoid hormones depress liver Δ5 desaturase activity through different mechanisms

Alaniz, María J. T. de; Marra, Carlos Alberto

doi:10.1007/bf02536117

Cited by 21 publications

(8 citation statements)

References 27 publications

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“…Previous experiments from our laboratory demonstrated that glucocorticoids can induce a soluble second messenger recovered as a low molecular weight peptide in the 110,000 × g supernatant fraction from liver cell homogenates. The addition of this factor modulates desaturase activities in in vitro enzyme assays (39,54,55). It was our aim to investigate if calcium deprivation could modify desaturase activity through a similar mechanism of action.…”

Section: Discussionmentioning

confidence: 99%

Calcium deficiency modifies polyunsaturated fatty acid metabolism in growing rats

Marra

Alaniz

2000

Lipids

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Fatty acid desaturase activities were determined in liver microsomes from calcium-deficient rats and compared to calcium-sufficient ones. The calcium-deprived diet (0.5 g/kg) administered for 60 d caused a 30% inhibition in the delta5 desaturase activity and a 45-55% decrease in delta6 and delta9, respectively, facts that cannot be attributed to a reduction in food intake. In vitro addition of calcium, ethyleneglycol-bis(Beta-aminoethyl ether)N,N-tetraacetic acid, and/or cytosol fractions from control or calcium-deficient rats to microsomes from both groups of animals indicates that the reduced desaturase capacities would be the consequence of an indirect effect of calcium deprivation. The present work shows that the reduced unsaturated fatty acid biosynthesis might be the result of modifications in the physicochemical properties of microsomal membranes. Such changes could also be derived from the inhibition of phospholipase A2 activity induced by calcium deficiency.

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Section: Discussionmentioning

confidence: 99%

Calcium deficiency modifies polyunsaturated fatty acid metabolism in growing rats

Marra

Alaniz

2000

Lipids

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“…Production of AA from LA involves three key enzymatic steps: Δ-6-desaturation to form 18:3n6 (GLA), followed by elongation to 20:3n6 (dihomo-GLA (DGLA)) and a Δ-5-desaturation step to produce 20:4n6. Thus, LA-enriched formulas cannot worsen inflammation simply because the activity of the enzymes Δ-5-desaturase and Δ-6-desaturase are severely compromised during critical illness by the release of stress and catabolic hormones (for example, glucocorticoids and catecholamines) [33,34] limiting the ability to form AA despite the provision of LA [35]. GLA is a metabolite of LA that can bypass the decreased expression of Δ-6-desaturase.…”

Section: Discussionmentioning

confidence: 99%

Enteral nutrition with eicosapentaenoic acid, γ-linolenic acid and antioxidants in the early treatment of sepsis: results from a multicenter, prospective, randomized, double-blinded, controlled study: the INTERSEPT Study

et al. 2011

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IntroductionEnteral nutrition (EN) with eicosapentaenoic acid (EPA)/γ-linolenic acid (GLA) is recommended for mechanically ventilated patients with severe lung injury. EPA/GLA has anti-inflammatory benefits, as evidenced by its association with reduction in pulmonary inflammation, improvement in oxygenation and improved clinical outcomes in patients with severe forms of acute lung injury. This study was a prospective, multicenter, randomized, double-blinded, controlled trial designed to investigate whether EPA/GLA could have an effective role in the treatment of patients with early sepsis (systemic inflammatory response syndrome with confirmed or presumed infection and without any organ dysfunction) by reducing the progression of the disease to severe sepsis (sepsis associated with at least one organ failure) or septic shock (sepsis associated with hypotension despite adequate fluid resuscitation). Secondary outcomes included the development of individual organ failure, increased ICU and hospital length of stay, need for mechanical ventilation and 28-day all-cause mortality.MethodsRandomization was concealed, and patients were allocated to receive, for seven days, either an EPA/GLA diet or an isocaloric, isonitrogenous control diet not enhanced with lipids. Patients were continuously tube-fed at a minimum of 75% of basal energy expenditure × 1.3. To evaluate the progression to severe sepsis and/or septic shock, daily screening for individual organ failure was performed. All clinical outcomes were recorded during a 28-day follow-up period.ResultsA total of 115 patients in the early stages of sepsis requiring EN were included, among whom 106 were considered evaluable. Intention-to-treat (ITT) analysis demonstrated that patients fed the EPA/GLA diet developed less severe sepsis and/or septic shock than patients fed the control diet (26.3% versus 50%, respectively; P = 0.0259), with similar results observed for the evaluable patients (26.4% versus 50.9% respectively; P = 0.0217). The ITT analysis demonstrated that patients in the study group developed cardiovascular failure (36.2% versus 21%, respectively; P = 0.0381) and respiratory failure (39.6% versus 24.6%, respectively; P = 0.0362) less often than the control group. Similarly, when considering only the evaluable patients, fewer patientsdeveloped cardiovascular failure (20.7% versus 37.7%, respectively; P = 0.03) and respiratory failure (26.4% versus 39.6%, respectively; P = 0.04). The percentage of patients fed the EPA/GLA diet requiring invasive mechanical ventilation was reduced compared with controls (ITT patients: 18.9% versus 33.9%, respectively; P = 0.394; evaluable patients: 17.5% versus 34.5%, respectively; P = 0.295). Patients nourished with the EPA/GLA diet remained in the ICU fewer days than the control population (ITT patients: 21.1 ICU-free days versus 14.7 ICU-free days, respectively; P < 0.0001; evaluable patients: 20.8 ICU-free days versus 14.3 ICU-free days, respectively; P < 0.0001) and fewer days at the hospital (ITT patients: 19.5 hospital-f...

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“…As discussed above, these outcomes may be attributable to several compounding factors. While ∆6 desaturation of both LNA to stearidonic acid (18:4n-3) and LA to GLA is a rate-limiting step under normal conditions, evidence exists to suggest that ∆6-desaturase activity is further reduced under conditions that foster release of epinephrine and other stress-associated hormones (29)(30)(31). This hormonal milieu can be found in traumatized or acutely septic patients.…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, formation of EPA from LNA is subject to the activity of ∆6 desaturase, a rate-limiting enzyme that catalyzes the initial desaturation of LNA to stearidonic acid (18:4n-3) (27,28). Compounding this quandary are reports that the stress hormones, i.e., epinephrine (29,30), ACTH (30) or glucocorticoids (31), have an inhibitory effect on both the ∆6 and ∆5 desaturases involved in LNA desaturation to EPA. Reduced activity of ∆6 desaturase may also limit GLA formation from dietary LA, potentially retarding formation of DHGLA and its metabolite, PGE 1 .…”

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confidence: 99%

Metabolism of dietary α‐linolenic acid vs. eicosapentaenoic acid in rat immune cell phospholipids during endotoxemia

Palombo¹,

DeMichele²,

Boyce³

et al. 1998

Lipids

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Short-term (i.e., 3 d) continuous enteral feeding of diets containing eicosapentaenoic (EPA) and gamma-linolenic (GLA) polyunsaturated fatty acids (PUFA) to endotoxemic rats reduces the levels of arachidonic acid (AA) and linoleic acid (LA) in alveolar macrophage (AM) and liver Kupffer and endothelial (K&E) cell phospholipids with attendant decreases in prostaglandin formation by these cells in vitro. Diets that contain alpha-linolenic acid (LNA) as a substrate for endogenous formation of EPA may not be as effective in facilitating these immune cell modifications given the limited activity of delta6 desaturase. In the present study we compared the effectiveness of an LNA-enriched diet vs. an (EPA + GLA)-enriched diet to displace phospholipid AA from AM and liver K&E cells in vivo in endotoxemic rats fed enterally for 3 or 6 d. We determined the fatty acid composition of AM and K&E cell phospholipids by gas chromatography. We found that AM and K&E cells from rats that had received the EPA + GLA diet for 3 d had significantly (P < 0.001) higher mole percentage of EPA and the GLA metabolite, dihomoGLA, than corresponding cells from rats given the LNA diet or a control diet enriched with LA. Rats given the LNA diet had relatively low levels of stearidonic acid, EPA and other n-3 PUFA, while rats given the LA diet had low levels of GLA and dihomoGLA. We conclude that diets enriched with LNA or LA may not be as effective as those enriched with EPA + GLA for purposes of fostering incorporation of EPA or dihomoGLA into and displacement of AA from macrophage phospholipids under pathophysiologic conditions commonly found in acutely septic patients.

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Glucocorticoid and mineralocorticoid hormones depress liver Δ5 desaturase activity through different mechanisms

Cited by 21 publications

References 27 publications

Calcium deficiency modifies polyunsaturated fatty acid metabolism in growing rats

Calcium deficiency modifies polyunsaturated fatty acid metabolism in growing rats

Enteral nutrition with eicosapentaenoic acid, γ-linolenic acid and antioxidants in the early treatment of sepsis: results from a multicenter, prospective, randomized, double-blinded, controlled study: the INTERSEPT Study

Metabolism of dietary α‐linolenic acid vs. eicosapentaenoic acid in rat immune cell phospholipids during endotoxemia

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