Neonatal interstitial lung disease in a girl with Jacobsen syndrome: a case report.

BACKGROUND: We report a case of the neonatal interstitial lung disease pulmonary interstitial glycogenosis in a girl with Jacobsen syndrome. While Jacobsen syndrome is caused by a deletion on the long arm of chromosome 11 and is genetically confirmed, pulmonary interstitial glycogenosis is of unknown etiology and is diagnosed by lung biopsy. Pulmonary interstitial glycogenosis has not previously been described in association with Jacobsen syndrome. CASE PRESENTATION: A term newborn small for gestational age Caucasian girl presented with respiratory distress, pulmonary hypertension, congenital heart defects, immunodeficiency, and thrombocytopenia. She was diagnosed with Jacobsen syndrome, but also had pulmonary interstitial glycogenosis, which contributed to significant morbidity. There was striking clinical improvement after steroid treatment of the pulmonary interstitial glycogenosis. CONCLUSIONS: Interstitial lung disease should be considered as a differential diagnosis when respiratory distress and hypoxemia in the perinatal period worsens or persists despite standard treatment. Importantly, pulmonary interstitial glycogenosis may be treatable with corticosteroids. Whether there is a genetic link between pulmonary interstitial glycogenosis and Jacobsen syndrome is still unknown.

Fish oil and the pan-PPAR agonist tetradecylthioacetic acid affect the amino acid and carnitine metabolism in rats.

Peroxisome proliferator-activated receptors (PPARs) are important in the regulation of lipid and glucose metabolism. Recent studies have shown that PPARα-activation by WY 14,643 regulates the metabolism of amino acids. We investigated the effect of PPAR activation on plasma amino acid levels using two PPARα activators with different ligand binding properties, tetradecylthioacetic acid (TTA) and fish oil, where the pan-PPAR agonist TTA is a more potent ligand than omega-3 polyunsaturated fatty acids. In addition, plasma L-carnitine esters were investigated to reflect cellular fatty acid catabolism. Male Wistar rats (Rattus norvegicus) were fed a high-fat (25% w/w) diet including TTA (0.375%, w/w), fish oil (10%, w/w) or a combination of both. The rats were fed for 50 weeks, and although TTA and fish oil had hypotriglyceridemic effects in these animals, only TTA lowered the body weight gain compared to high fat control animals. Distinct dietary effects of fish oil and TTA were observed on plasma amino acid composition. Administration of TTA led to increased plasma levels of the majority of amino acids, except arginine and lysine, which were reduced. Fish oil however, increased plasma levels of only a few amino acids, and the combination showed an intermediate or TTA-dominated effect. On the other hand, TTA and fish oil additively reduced plasma levels of the L-carnitine precursor γ-butyrobetaine, as well as the carnitine esters acetylcarnitine, propionylcarnitine, valeryl/isovalerylcarnitine, and octanoylcarnitine. These data suggest that while both fish oil and TTA affect lipid metabolism, strong PPARα activation is required to obtain effects on amino acid plasma levels. TTA and fish oil may influence amino acid metabolism through different metabolic mechanisms.

Krill oil versus fish oil in modulation of inflammation and lipid metabolism in mice transgenic for TNF-α.

PURPOSE: Biological effects of marine oils, fish oil (FO) and krill oil (KO), are mostly attributed to the high content of n-3 polyunsaturated fatty acids (n-3 PUFAs), predominantly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). The study was aimed to investigate the influence of FO and KO on lipid homeostasis and inflammation in an animal model of persistent low-grade exposure to human tumor necrosis factor α (hTNF-α) and to evaluate whether these effects depend on the structural forms of EPA and DHA [triacylglycerols (TAG) vs. phospholipids]. METHODS: Male C57BL/6 hTNF-α mice were fed for 6 weeks a high-fat control diet (24.50 % total fats, w/w) or high-fat diets containing either FO or KO at similar doses of n-3 PUFAs (EPA: 5.23 vs. 5.39 wt%, DHA: 2.82 vs. 2.36 wt% of total fatty acids). RESULTS: We found that KO, containing bioactive n-3 PUFAs in the form of phospholipids, was capable of modulating lipid metabolism by lowering plasma levels of TAG and cholesterol and stimulating the mitochondrial and peroxisomal fatty acid ß-oxidation, as well as improving the overall carnitine turnover. Though the administration of FO was not as effective as KO in the lowering of plasma TAG, FO significantly improved the levels of all cholesterol classes in plasma. Except from the increase in the levels of IL-17 in FO-fed mice and a trend to decrease in MCP-1 levels in KO-fed animals, the levels of pro-inflammatory cytokines were not substantially different between treatment groups. CONCLUSION: Our findings demonstrate that FO and KO are comparable dietary sources of n-3 PUFAs. However, when quantitatively similar doses of n-3 PUFAs are administered, KO seems to have a greater potential to promote lipid catabolism. The effect of dietary oils on the levels of inflammatory markers in hTNF-α transgenic mice fed a high-fat diet needs further investigations.

Free carnitine and acylcarnitines in obese patients with polycystic ovary syndrome and effects of pioglitazone treatment.

OBJECTIVE: To determine fasting and insulin-stimulated levels of carnitine precursors, total and free carnitine, and acylcarnitines, and evaluate the impact of pioglitazone treatment in obese patients with polycystic ovary syndrome (PCOS). DESIGN: The present study is a secondary analysis of a previously published case-control study, followed by a double-blind randomized clinical trial. SETTING: Academic tertiary care medical center. PATIENT(S): Thirty obese premenopausal patients with PCOS and 14 healthy women. INTERVENTION(S): Sixteen weeks of blinded treatment with pioglitazone (30 mg/d) or placebo. MAIN OUTCOME MEASURE(S): Total and free carnitine and acylcarnitines. RESULT(S): Contrary to controls, patients with PCOS were characterized with slightly lower levels of fasting total and free carnitine, its precursors, and derivatives. Total and free carnitine correlated inversely to sex hormone-binding globulin (SHBG) in patients with PCOS, whereas no associations were found between acylcarnitines and androgenes. Insulin stimulation-induced changes in the levels of total and free carnitine, carnitine precursors, and acylcarnitines in the PCOS group followed the same trends as in the control group. Pioglitazone treatment significantly increased fasting levels of serum-free carnitine, propionyl carnitine, and total carnitine. The analysis of between group differences revealed significant changes in the isovaleryl carnitine levels and lipid oxidation rates after pioglitazone treatment compared with placebo. CONCLUSION(S): Acute insulin stimulation was associated with increased serum levels of free carnitine in both patients and healthy controls. Treatment with pioglitazone is able to redistribute free fatty acids from insulin-sensitive tissues, diminish demand for carnitine, and influence the overall carnitine turnover. CLINICAL TRIAL REGISTRATION NUMBER: NCT00145340.

Krill powder increases liver lipid catabolism and reduces glucose mobilization in tumor necrosis factor-alpha transgenic mice fed a high-fat diet.

A promising approach to ameliorate obesity and obesity-associated diseases is the identification of new sources of dietary ingredients. The present study investigated the hepatic regulation of energy metabolism after feeding a powder isolated from Antarctic krill (Euphausia superba) in a transgenic mouse model of chronic inflammation (human tumor necrosis factor-alpha (hTNFα) mice) known to display unfavorable effects on lipid metabolism. Male hTNFα mice were fed high-fat diets (23.6%, w/w) with or without krill powder (6.4% lipids, 4.3% protein, w/w) for 6 weeks. Blood, liver lipid, and fatty acid composition, as well as hepatic enzyme activities and gene expressions, were determined. Krill powder fed mice displayed lowered hepatic and plasma triacylglycerol levels compared to mice on a high-fat casein diet. This was accompanied by down-regulated hepatic expression of genes involved in lipogenesis and glycerolipid synthesis, and increased ß-oxidation activity. In addition, the krill powder diet lowered plasma levels of cholesterol, as well as hepatic gene expression of sterol regulatory element binding transcription factor 2 (SREBP2) and enzymes involved in cholesterol synthesis. Notably, genes involved in glycolysis and gluconeogenesis were significantly reduced in liver by the krill powder diet, while genes involved in oxidative phosphorylation and uncoupling were not affected. Krill powder also reduced endogenous TNFα in liver, indicating an anti-inflammatory effect. In a high-fat mouse model with disturbed lipid metabolism due to persistent hTNFα expression, krill powder showed significant effects on hepatic glucose- and lipid metabolism, resulting in an improved lipid status in liver and plasma.

Fish oil and 3-thia fatty acid have additive effects on lipid metabolism but antagonistic effects on oxidative damage when fed to rats for 50 weeks.

The 3-thia fatty acid tetradecylthioacetic acid (TTA) is a synthetic modified fatty acid, which, similar with dietary fish oil (FO), influences the regulation of lipid metabolism, the inflammatory response and redox status. This study was aimed to penetrate the difference in TTA's mode of action compared to FO in a long-term experiment (50 weeks of feeding). Male Wistar rats were fed a control, high-fat (25% w/v) diet or a high-fat diet supplemented with either TTA (0.375% w/v) or FO (10% w/v) or their combination. Plasma fatty acid composition, hepatic lipids and expression of relevant genes in the liver and biomarkers of oxidative damage to protein were assessed at the end point of the experiment. Both supplements given in combination demonstrated an additive effect on the decrease in plasma cholesterol levels. The FO diet alone led to removal of plasma cholesterol and a concurrent cholesterol accumulation in liver; however, with TTA cotreatment, the hepatic cholesterol level was significantly reduced. Dietary FO supplementation led to an increased oxidative damage, as seen by biomarkers of protein oxidation and lipoxidation. Tetradecylthioacetic acid administration reduced the levels of these biomarkers confirming its protective role against lipoxidation and protein oxidative damage. Our findings explore the lipid reducing effects of TTA and FO and demonstrate that these bioactive dietary compounds might act in a different manner. The experiment confirms the antioxidant capacity of TTA, showing an improvement in FO-induced oxidative stress.