A functional variant in the Stearoyl-CoA desaturase gene promoter enhances fatty acid desaturation in pork

There is growing public concern about reducing saturated fat intake. Stearoyl-CoA desaturase (SCD) is the lipogenic enzyme responsible for the biosynthesis of oleic acid (18:1) by desaturating stearic acid (18:0). Here we describe a total of 18 mutations in the promoter and 3′ non-coding region of the pig SCD gene and provide evidence that allele T at AY487830:g.2228T>C in the promoter region enhances fat desaturation (the ratio 18:1/18:0 in muscle increases from 3.78 to 4.43 in opposite homozygotes) without affecting fat content (18:0+18:1, intramuscular fat content, and backfat thickness). No mutations that could affect the functionality of the protein were found in the coding region. First, we proved in a purebred Duroc line that the C-T-A haplotype of the 3 single nucleotide polymorphisms (SNPs) (g.2108C>T; g.2228T>C; g.2281A>G) of the promoter region was additively associated to enhanced 18:1/18:0 both in muscle and subcutaneous fat, but not in liver. We show that this association was consistent over a 10-year period of overlapping generations and, in line with these results, that the C-T-A haplotype displayed greater SCD mRNA expression in muscle. The effect of this haplotype was validated both internally, by comparing opposite homozygote siblings, and externally, by using experimental Duroc-based crossbreds. Second, the g.2281A>G and the g.2108C>T SNPs were excluded as causative mutations using new and previously published data, restricting the causality to g.2228T>C SNP, the last source of genetic variation within the haplotype. This mutation is positioned in the core sequence of several putative transcription factor binding sites, so that there are several plausible mechanisms by which allele T enhances 18:1/18:0 and, consequently, the proportion of monounsaturated to saturated fat.

Sleep desaturation and its relationship to lung function, exercise and quality of life in LAM

Background: Lymphangioleiomyomatosis (LAM) is characterised by progressive airway obstruction and hypoxaemia in young women. Although sleep may trigger hypoxaemia in patients with airway obstruction, it has not been previously investigated in patients with LAM. Methods: Consecutive women with lung biopsy proven LAM and absence of hypoxaemia while awake were evaluated with pulmonary function test, echocardiography, 6-min walk test, overnight full polysomnography, and Short Form 36 health-related quality-of-life questionnaire. Results: Twenty-five patients with (mean +/- SD) age 45 +/- 10 years, SpO(2) awake 95% +/- 2, forced expiratory volume in the first second (median-interquartile) FEV1 (% predicted) 77 (47-90) and carbonic monoxide diffusion capacity, DLCO (%) 55 (34-74) were evaluated. Six-minute walk test distance and minimum SpO(2) (median-interquartile) were, respectively, 447 m (411 -503) and 90% (82-94). Median interquartile apnoea-hypopnoea index was in the normal range 2 (1-5). Fourteen patients (56%) had nocturnal hypoxaemia (10% total sleep time with SpO(2) <90%), and the median sleep time spent with SpO(2) <90% was 136 (13-201) min. Sleep time spent with SpO(2) <90% correlated with the residual volume/total lung capacity ratio (r(s) = 0.5, p: 0.02), DLCO (r(s) = -0.7, p: 0.001), FEV1 (r(s) = -0.6, p: 0.002). Multivariate linear regression model showed that RV/TLC ratio was the most important functional variable related to sleep hypoxaemia. Conclusion: Significant hypoxaemia during sleep is common in LAM patients with normal SpO(2) while awake, especially among those with some degree of hyperinflation in lung function tests. (C) 2011 Published by Elsevier Ltd.

Immunocytochemical localization of acyl-lipid desaturases in cyanobacterial cells: evidence that both thylakoid membranes and cytoplasmic membranes are sites of lipid desaturation.

There are four acyl-lipid desaturases in the cyanobacterium Synechocystis sp. PCC 6803. Each of these desaturases introduces a double bond at a specific position, such as the Delta6, Delta9, Delta12, or omicron3 position, in C18 fatty acids. The localization of the desaturases in cyanobacterial cells was examined immunocytochemically with antibodies raised against synthetic oligopeptides that corresponded to the carboxyl-terminal regions of the desaturases. All four desaturases appeared to be located in the regions of both the cytoplasmic and the thylakoid membranes. These findings suggest that fatty acid desaturation of membrane lipids takes place in the thylakoid membranes as well as in the cytoplasmic membranes.

Propofol-induced sleep: Polysomnographic evaluation of patients with obstructive sleep apnea and controls

OBJECTIVE: The localization of upper airway obstruction in patients with obstructive sleep apnea (OSA) may optimize treatment. Nasoendoscopy during propofol sedation allows such an evaluation, but the effect of this drug on respiratory patterns and muscle relaxation is unknown. The objective of the present study was to determine through polysomnography whether propofol would change sleep parameters. STUDY DESIGN: Prospective study of subjects submitted to polysomnography under sedation with propofol. SETTING: Tertiary referral center. SUBJECTS AND METHODS: Fifteen non-obese subjects (4 controls/11 OSA patients) were submitted to two diurnal polysomnograms (90-120 minutes of sleep), with and without the use of propofol. The parameters presence of snoring, apnea-hypopnea index (AHI), oxygen desaturation, and sleep architecture were compared. RESULTS: The use of propofol did not induce snoring in the control subjects, whereas 100 percent of the OSA patients snored. AHI and mean oxygen saturation (SaO(2)) did not differ significantly between examinations with and without sedation. However, minimum SaO(2) differed significantly (P < 0.05) with sedation, being lower during propofol sedation. Propofol also significantly changed the sleep architecture, with a significant increase in N3 sleep (P < 0.005) and total abolishment of rapid eye movement sleep (P < 0.0005) during propofol sedation. CONCLUSIONS: These preliminary results allow us to infer that sedation with propofol changes sleep architecture but permits respiratory evaluation, because the main respiratory parameters evaluated in OSA are maintained. These preliminary results support the view that nasoendoscopy under propofol sedation is a promising examination for management of this disease. (C) 2010 American Academy of Otolaryngology-Head and Neck Surgery Foundation. All rights reserved.

Obstructive Sleep Apnea An Emerging Risk Factor for Atherosclerosis

Obstructive sleep apnea (OSA) is independently associated with death from cardiovascular diseases, including myocardial infarction and stroke. Myocardial infarction and stroke are complications of atherosclerosis; therefore, over the last decade investigators have tried to unravel relationships between OSA and atherosclerosis. OSA may accelerate atherosclerosis by exacerbating key atherogenic risk factors. For instance, OSA is a recognized secondary cause of hypertension and may contribute to insulin resistance, diabetes, and dyslipidemia. In addition, clinical data and experimental evidence in animal models suggest that OSA can have direct proatherogenic effects inducing systemic inflammation, oxidative stress, vascular smooth cell activation, increased adhesion molecule expression, monocyte/lymphocyte activation, increased lipid loading in macrophages, lipid peroxidation, and endothelial dysfunction. Several cross-sectional studies have shown consistently that OSA is independently associated with surrogate markers of premature atherosclerosis, most of them in the carotid bed. Moreover, OSA treatment with continuous positive airway pressure may attenuate carotid atherosclerosis, as has been shown in a randomized clinical trial. This review provides an update on the role of OSA in atherogenesis and highlights future perspectives in this important research area. CHEST 2011; 140(2):534-542

Factores que influenciam a actividade física na vida diária dos doentes com doença pulmonar obstrutiva crónica

RESUMO: A monitorização da actividade física diária nos doentes com Doença Pulmonar Obstrutiva Crónica (DPOC) tem sido alvo de grande interesse nos últimos tempos. No entanto, ainda nenhum estudo reuniu o conjunto de factores – grau de obstrução, hiperinsuflação pulmonar, alteração das trocas gasosas, dispneia, dessaturação de oxigénio, capacidade de exercício, ansiedade e depressão – que podem afectar a sua realização, nem os correlacionou com os dados obtidos com o pedómetro e que reflectem o que cada doente realmente faz no seu dia-adia. O presente estudo teve como objectivo principal identificar os factores que influenciam a actividade física na vida diária dos doentes com DPOC. Estudaram-se 55 doentes do sexo masculino com idade média de 67 anos e um FEV1 médio de 50,8% do previsto, com DPOC moderada a muito grave (estadios II a IV), de entre os utentes do Laboratório de Fisiopatologia Respiratória do Centro Hospitalar de Torres Vedras. Avaliaram-se os parâmetros da escala de dispneia modificada do Medical Research Council (MMRC), escala London Chest Activity of Daily Living (LCADL), escala de Ansiedade e Depressão Hospitalar (HADS), índice BODE, estudo funcional respiratório em repouso, teste de marcha de seis minutos e o número de passos por dia utilizando um pedómetro por um período de três dias. Observou-se que os doentes deram em média 4972 passos por dia e apresentaram uma cotação total média de 17,7 na LCADL, tendo existido diferenças estatisticamente significativas em função da gravidade da doença, sendo que os doentes mais graves são os que em média andam menos no seu dia-a-dia e apresentam maior limitação na realização das actividades de vida diária. O número de passos por dia apresentou correlações significativas com as variáveis idade, dispneia, depressão, hiperinsuflação monar, gravidade de obstrução (FEV1), trocas gasosas (DLCO), saturação arterial de oxigénio mínima e correlação mais forte com a distância percorrida no TM6m. Este estudo permitiu identificar que os factores determinantes da actividade física na vida diária de doentes com DPOC nos estadios II a IV, foram a dispneia e a distância percorrida no TM6m. Além disso, estes doentes constituem um grupo sedentário, particularmente a partir do estadio III, com níveis de actividade física diária baixos.-----------ABSTRACT There has been an increased interest in monitoring the daily physical activity in patients with Chronic Obstructive Pulmonary Disease (COPD). However, no specific study has been realized so far that has put the different factors which can affect the results obtained altogether, (such as the degree of obstruction, pulmonary hyperinflation, abnormal gas exchange, dyspnea, oxygen desaturation, exercise capacity, anxiety and depression) or correlated with data obtained from the pedometer, which reflect each patient actual activity in their daily life. This study aimed to identify the main factors that influence physical activity in daily life of patients with COPD. The scope of this study was 55 male patients with an average age of 67 years old and an average FEV1 of 50.8% predicted, with moderate to severe COPD (stages II to IV), among patients from the Respiratory Pathophysiology Laboratory of the Centro Hospitalar de Torres Vedras. Were evaluated the parameters of the modified Medical Research Council dyspnea scale (MMRC), London Chest Activity of Daily Living scale (LCADL), Hospital Anxiety and Depression scale (HADS), BODE index, pulmonary function test at rest, six minute walk test (6MWT) and the number of steps per day using a pedometer for a period of three days. It was observed that patients have walked an average of 4972 steps per day and had a total score of 17.7 at LCADL, and statistically significant differences were stated depending on the severity of the disease. Whereas patients with a more severe degree of the disease have walked least in their daily life and show greater restraint in carrying out activities of daily living. The number of steps per day showed significant correlations with age, dyspnea, depression, lung hyperinflation, severity of obstruction (FEV1), gas exchange (DLCO), minimum arterial oxygen saturation and stronger correlation with distance walked on 6MWT. This study shows that the crucial factors of physical activity in daily life of COPD patients at stages II to IV were dyspnea and distance on 6MWT. Moreover, these patients constitute a sedentary group, particularly from the stage III, with lower levels of daily physical activity.

Oximetry alone versus portable polygraphy for sleep apnea screening before bariatric surgery.

BACKGROUND: Screening for obstructive sleep apnea (OSA) is recommended as part of the preoperative assessment of obese patients scheduled for bariatric surgery. The objective of this study was to compare the sensitivity of oximetry alone versus portable polygraphy in the preoperative screening for OSA. METHODS: Polygraphy (type III portable monitor) and oximetry data recorded as part of the preoperative assessment before bariatric surgery from 68 consecutive patients were reviewed. We compared the sensitivity of 3% or 4% desaturation index (oximetry alone) with the apnea-hypopnea index (AHI; polygraphy) to diagnose OSA and classify the patients as normal (<10 events per hour), mild to moderate (10-30 events per hour), or severe (>30 events per hour). RESULTS: Using AHI, the prevalence of OSA (AHI > 10 per hour) was 57.4%: 16.2% of the patients were classified as severe, 41.2% as mild to moderate, and 42.6% as normal. Using 3% desaturation index, 22.1% were classified as severe, 47.1% as mild to moderate, and 30.9% as normal. With 4% desaturation index, 17.6% were classified as severe, 32.4% as mild, and 50% as normal. Overall, 3% desaturation index compared to AHI yielded a 95% negative predictive value to rule out OSA (AHI > 10 per hour) and a 100% sensitivity (0.73 positive predictive value) to detect severe OSA (AHI > 30 per hour). CONCLUSIONS: Using oximetry with 3% desaturation index as a screening tool for OSA could allow us to rule out significant OSA in almost a third of the patients and to detect patients with severe OSA. This cheap and widely available technique could accelerate preoperative work-up of these patients.

Increasing respiratory dead space improves sleep disordered breathing and hypoxemia in patients with chronic mountain sickness

Background: Chronic mountain sickness (CMS), which is characterised by hypoxemia, erythrocytosis and pulmonary hypertension, is a major public health problem in high-altitude dwellers. The only existing treatment is descent to low altitude, an option that for social reasons almost never exists. Sleep disordered breathing may represent an underlying mechanism. We recently found that in mountaineers increasing the respiratory dead space markedly improves sleep disordered breathing. The aim of the present study was to assess the effects of this procedure on sleep disordered breathing in patients with CMS. Methods: In 10 male Bolivian high-altitude dwellers (mean ± SD age, 59 ± 9 y) suffering from CMS (haemoglobin >20 g/L) full night sleep recordings (Embletta, RespMed) were obtained in La Paz (3600 m). In random order, one night was spent with a 500 ml increase in dead space through a custom designed full face mask and the other night without it. Exclusion criteria were: secondary erythrocytosis, smoking, drug intake, acute infection, cardio- pulmonary or neurologic disease and travelling to low altitude in the preceding 6 months. Results: The major new finding was that added dead space dramatically improved sleep disordered breathing in patients suffering from CMS. The apnea/hypopnea index decreased by >50% (from 34.5 ± 25.0 to 16.8 ± 14.9, P = 0.003), the oxygen desaturation index decreased from 46.2 ± 23.0 to 27.2 ± 20.0 (P = 0.0004) and hypopnea index from 28.8 ± 20.9 to 16.3 ± 14.0 (P = 0.01), whereas nocturnal oxygen saturation increased from 79.8 ± 3.6 to 80.9 ± 3.0% (P = 0.009). The procedure was easily accepted and well tolerated. Conclusion: Here, we show for the very first time that an increase in respiratory dead space through a fitted mask dramatically improves nocturnal breathing in high-altitude dwellers suffering from CMS. We speculate that when used in the long-term, this procedure will improve erythrocytosis and pulmonary hypertension and offer an inexpensive and easily implementable treatment for this major public health problem.

Effects of added dead space on sleep disordered breathing at high altitude

Introduction: Sleep disordered breathing with central apnea or hypopnea frequently occurs during sleep at high altitude. The aim of this study was to assess the effects of added dead space (DS) on sleep disordered breathing and transcutaneous CO2 (PtcCO2) level during sleep at high altitude. Methods: Full night sleep recordings were obtained on 12 unacclimatized mountaineers (11 males, 1 female, mean age 39 ± 12 y.o.) during one of the first 4 nights after arrival in Leh, Ladakh (3500 m). In random order, half of the night was spent with a 500 ml increase in dead space through a custom designed full face mask and the other half without it. PtcCO2 was measured in 3 participants. Results: Baseline recordings reveled two clearly distinct groups: one with severe sleep disordered breathing (n = 5) and the other with mild or no disordered breathing (n = 7). Added dead space markedly improved breathing in the first group (baseline vs DS): apnea hypopnea index (AHI) 70.3 ± 25.8 vs 29.4 ± 6.9 (p = 0.013), oxygen desaturation index (ODI): 72.9 ± 24.1/h vs 42.5 ± 14.4 (p = 0.031), whereas it had no significant effect in the second group. Added dead space did not have a significant effect on mean oxygen saturation level. Respiratory events were almost exclusively central apnea or hypopnea except for one subject. Only a minor increase in mean PtcCO2 (n = 3) was observed: 33.6 ± 1.8 mm Hg at baseline and 35.0 ± 2.62 mm Hg with DS. Sleep quality was preserved under dead space condition, since the microarousal rate remained unchanged (16.8 ± 8.7/h vs 19.4 ± 18.6/h (p = 0.51). Conclusion: In mountaineers with severe sleep disordered breathing at high altitude, a 500 ml increase in dead space through a fitted mask significantly improves nocturnal breathing.

Effects of dietary protein type on oxidized cholesterol-induced alteration in age-related modulation of lipid metabolism and indices of immune function in rats.

Exogenous oxidized cholesterol disturbs both lipid metabolism and immune functions. Therefore, it may perturb these modulations with ageing. Effects of the dietary protein type on oxidized cholesterol-induced modulations of age-related changes in lipid metabolism and immune function was examined using differently aged (4 weeks versus 8 months) male Sprague-Dawley rats when casein, soybean protein or milk whey protein isolate (WPI) was the dietary protein source, respectively. The rats were given one of the three proteins in diet containing 0.2% oxidized cholesterols mixture. Soybean protein, as compared with the other two proteins, significantly lowered both the serum thiobarbituric acid reactive substances value and cholesterol, whereas it elevated the ratio of high density lipoprotein-cholesterol/cholesterol in young rats, but not in adult. Moreover, soybean protein, but not casein and WPI, suppressed the elevation of Delta6 desaturation indices of phospholipids in both liver and spleen, particularly in young. On the other hand, WPI, compared to the other two proteins, inhibited the leukotriene B4 production of spleen, irrespective of age. Soybean protein reduced the ratio of CD4(+)/CD8(+) T-cells in splenic lymphocytes. Therefore, the levels of immunoglobulin (Ig)A, IgE and IgG in serum were lowered in rats given soybean protein in both age groups except for IgA in adult, although these observations were not shown in rats given other proteins. Thus, various perturbations of lipid metabolism and immune function caused by oxidized cholesterol were modified depending on the type of dietary protein. The moderation by soybean protein on the change of lipid metabolism seems to be susceptible in young rats whose homeostatic ability is immature. These observations may be exerted through both the promotion of oxidized cholesterol excretion to feces and the change of hormonal release, while WPI may suppress the disturbance of immune function by oxidized cholesterol in both ages. This alleviation may be associated with a large amount of lactoglobulin in WPI. These results thus showed a possibility that oxidized cholesterol-induced perturbations of age-related changes of lipid metabolism and immune function can be moderated by both the selection and combination of dietary protein.

Papilledema and obstructive sleep apnea syndrome.

OBJECTIVES: To characterize the pathogenesis and clinical features of optic disc edema associated with obstructive sleep apnea syndrome (SAS). METHODS: A series of 4 patients with SAS and papilledema (PE) underwent complete neuro-ophthalmologic evaluation and lumbar puncture. In 1 patient, continuous 24-hour intracranial pressure (ICP) monitoring was also performed. RESULTS: All 4 patients had bilateral PE that was asymmetric in 2. Three patients had optic nerve dysfunction, asymmetric in 1, unilateral in 2. Daytime cerebrospinal fluid pressure measurements were within normal range. Nocturnal monitoring performed in one patient, however, demonstrated repeated episodes of marked ICP elevation associated with apnea and arterial oxygen desaturation. CONCLUSIONS: We propose that PE in SAS is due to episodic nocturnal hypoxemia and hypercarbia resulting in increased ICP secondary to cerebral vasodilation. In these individuals, intermittent ICP elevation is sufficient to cause persistent disc edema. These patients may be at increased risk for developing visual loss secondary to PE compared with patients with obesity-related pseudotumor cerebri because of associated hypoxemia. The diagnosis of SAS PE may not be appreciated because daytime cerebrospinal fluid pressure measurements are normal and because patients tend to present with visual loss rather than with symptoms of increased ICP.

Reproduction, fat metabolism, and life span: what is the connection?

Reduced reproduction is associated with increased fat storage and prolonged life span in multiple organisms, but the underlying regulatory mechanisms remain poorly understood. Recent studies in several species provide evidence that reproduction, fat metabolism, and longevity are directly coupled. For instance, germline removal in the nematode Caenorhabditis elegans promotes longevity in part by modulating lipid metabolism through effects on fatty acid desaturation, lipolysis, and autophagy. Here, we review these recent studies and discuss the mechanisms by which reproduction modulates fat metabolism and life span. Elucidating the relationship between these processes could contribute to our understanding of age-related diseases including metabolic disorders.

Stable carbon isotope composition of perirenal adipose tissue fatty acids from Engadine sheep grazing either mountain or lowland pasture

To provide further insights into ruminant lipid digestion and metabolism, and into cis9, trans-11 18:2 synthesis, 12 growing Engadine lambs grazing either mountain pasture (2,250 m above sea level; n = 6) or lowland pasture (400 m above sea level; n = 6) were studied. Both pastures consisted exclusively of C-3 plants. Before the experiment, all animals grazed a common pasture for 6 wk. Grasses and perirenal adipose tissues of the sheep were analyzed for fatty acids by gas chromatography. Stable C-isotope ratios (delta C-13 values in % vs. the Vienna Pee Dee Belemnite standard) were determined in the composite samples by elemental analysis-isotope ratio mass spectrometry. The delta C-13 of the individual fatty acids were measured by gas chromatography-combustion-isotope ratio mass spectrometry. The delta C-13 value of the entire mountain pasture grass was -27.5% (SD 0.31), whereas that of the lowland pasture grass was -30.0% (SD 0.07). This difference was reflected in the perirenal adipose tissues of the corresponding sheep (P < 0.05), even though the delta C-13 values were less in the animals than in the grass. The delta C-13 values for cis-9 16:1 and cis-9 18:1 in perirenal fat differed between mountain and lowland lambs (P < 0.05). The 16:0 in the adipose tissue was enriched in C-13 by 5% compared with the dietary 16:0, likely as a result of partly endogenous synthesis. The d13C values of cis-9, trans-11 18:2 (cis-9, trans-11 CLA) in the adipose tissue were smaller than those of its dietary precursors, cis-9, cis-12 18:2 and cis-9, cis-12, cis-15 18:3; conversely, the delta C-13 values of trans-11 18:1 were not, suggesting that large proportions of perirenal cis-9, trans-11 18:2 were of endogenous origin and discrimination against C-13 occurred during Delta(9)-desaturation. The same discrimination was indicated by the isotopic shift between 16:0 and cis-9 16:1 in the mountain grazing group. Furthermore, the delta C-13 values of cis-9, trans-11 18:2 were smaller relative to the precursor fatty acids in the mountain lambs compared with the lowland group. This result suggests a reduced extent of biohydrogenation in lambs grazing on mountain grass in comparison with those grazing on lowland grass. This was supported by the smaller cis-9, trans-11 18:2 concentrations in total fatty acids found in the adipose tissues of the lowland lambs (P < 0.001). The results of this study demonstrate that natural differences between delta C-13 values of swards from different pastures and the adipose tissue fatty acids could be used as tracers in studies of lipid metabolism in ruminants.

Dépistage du syndrome des apnées du sommeil [Screening for sleep apnea syndrome]

Sleep apnea syndrome (SAS) consists of nocturnal snoring interrupted by obstructive apnea and of diurnal symptoms like hypersomnolence as a consequence of sleep fragmentation. Cardiovascular morbidity and mortality associated with this syndrome justify early detection and appropriate treatment. Polysomnography is still a frequently used method for early detection; however, several disadvantages like duration, discomfort and expense led to a search for alternatives. Since the beginning of the eighties, oximetry allows recording of nocturnal oxygen saturation of hemoglobin even at home. Nocturnal oximetry reveals O2-desaturation associated with apnea and thus permits often to diagnose or exclude SAS. Diagnosis of SAS is made when at least 20 desaturations per hour with an amplitude of at least 4% are recorded. On the other hand, normal nocturnal oximetry nearly excludes SAS. In those cases where nocturnal oximetry is not diagnostic, polysomnography remains the method of choice. Departing from published work, a model for SAS detection, based mainly on nocturnal oximetry, is proposed.