Altered levels of serum sphingomyelin and ceramide containing distinct acyl chains in young obese adults

Hanamatsu, Hisatoshi; Ohnishi, Shunsuke; Sakaï, Shota; Yuyama, Ken‐ichi; Mitsutake, Susumu; Takeda, Hiroshi; Hashino, Satoshi; Igarashi, Yasuyuki

doi:10.1038/nutd.2014.38

Cited by 140 publications

(114 citation statements)

References 34 publications

(43 reference statements)

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“…We observed increased levels of plasma SM 18:0 during late gestation in preeclamptic patients which is in line with previous reports describing elevated levels of SM 18:0 in term plasma of early-onset preeclamptic patients [42] and as well as in human PE placentae when compared with control subjects [43]. Recent studies have demonstrated that serum elevation of this particular class of sphingomyelin positively correlates with parameters of insulin resistance and liver function in obese adults [44] and correlates with markers of NF-kB activation and thus markers of intracellular inflammation [44]. It is well-documented in the literature that increased high plasma sphingomyelin levels are associated with subclinical atherosclerosis and coronary artery disease [24].…”

Section: Discussionsupporting

confidence: 92%

Plasma cross-gestational sphingolipidomic analyses reveal potential first trimester biomarkers of preeclampsia

et al. 2017

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IntroductionPreeclampsia (PE) is a gestational disorder, manifested in the second half of pregnancy by maternal hypertension, proteinuria and generalized edema. PE is a major cause of maternal and fetal morbidity and mortality, accounting for nearly 40% of all premature births worldwide. Bioactive sphingolipids are emerging as key molecules involved in etiopathogenesis of PE, characterized by maternal angiogenic imbalance and symptoms of metabolic syndrome. The aim of this study was to compare the cross-gestational profile of circulating bioactive sphingolipids in maternal plasma from preeclamptic (PE) versus normotensive control (CTL) subjects with the goal of identifying sphingolipids as candidate first trimester biomarkers of PE for early prediction of the disease.MethodsA prospective cohort of patients was sampled at the first, second and third trimester of pregnancy for each patient (11–14, 22–24, and 32–36 weeks´ gestation). A retrospective stratified study design was used to quantify different classes of sphingolipids in maternal plasma. We used a reverse-phase high-performance liquid chromatography-tandem mass spectrometry (HPLC-ESI-MS/MS) approach for determining different sphingolipid molecular species (sphingosine-1-phosphate (S1P), dihydro-sphingosine-1-phosphate (DH-S1P), sphingomyelins (SM) and ceramides (Cer)) in cross-gestational samples of human plasma from PE (n = 7, 21 plasma samples across pregnancy) and CTL (n = 7, 21 plasma samples across pregnancy) patients.ResultsPlasma levels of angiogenic S1P did not change significantly in control and in preeclamptic patients´ group across gestation. DH-S1P was significantly decreased in second trimester plasma of PE patients in comparison to their first trimester, which could contribute to reduced endothelial barrier observed in PE. The major ceramide species (Cer 16:0 and Cer 24:0) tended to be up-regulated in plasma of control and PE subjects across gestation. The levels of a less abundant plasma ceramide species (Cer 14:0) were significantly lower in first trimester plasma of PE patients when compared with their gestational-matched control samples (p = 0.009). Major plasma sphingomyelin species (SM 16:0, SM 18:1 and SM 24:0) tended to be higher in control pregnancies across gestation. However, in PE patients, SM 16:0, SM 18:0 and SM 18:1 showed significant up-regulation across gestation, pointing to atherogenic properties of the sphingomyelins and particularly the potential contribution of SM 18:0 to the disease development. In addition, two major sphingomyelins, SM 16:0 and SM 18:0, were significantly lower in first trimester plasma of PE patients versus first trimester samples of respective controls (p = 0.007 and p = 0.002, respectively).ConclusionsCross-gestational analysis of maternal plasma of preeclamptic and normotensive women identifies differences in the biochemical profile of major sphingolipids (DH-S1P, sphingomyelins and ceramides) between these two groups. In addition, first trimester maternal plasma sphingolipids (Cer 14:0, SM 16:0 an...

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Section: Discussionsupporting

confidence: 92%

Plasma cross-gestational sphingolipidomic analyses reveal potential first trimester biomarkers of preeclampsia

et al. 2017

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“…Most noteworthy, however, was the observation that athletes had significantly less basal serum C18:0 sphingomyelin than T2D. There is reason to believe that C18:0 sphingomyelin is particularly deleterious for insulin sensitivity in humans (14,22) and may serve as novel biomarker in this regard. Furthermore, serum sphingomyelin decreased in recovery from exercise with a similar response in most species.…”

Section: Discussionmentioning

confidence: 92%

“…Metabolomic profiling has helped clarify this discrepancy by associating certain sphingomyelin species, rather than total concentration, with metabolic parameters. For example, sphingomyelin 18:0, 20:0, 22:0, and 24:0 were associated with higher BMI and lower insulin sensitivity (14,22), whereas serum sphingomyelin 16:1 was related to enhanced insulin sensitivity and lower risk for diabetes (10). Thus, like most lipids, sphingomyelins are heterogeneous and have different effects related to acyl chain composition.…”

Section: Discussionmentioning

confidence: 99%

Serum sphingolipids: relationships to insulin sensitivity and changes with exercise in humans

Bergman

Brozinick

Strauss

et al. 2015

American Journal of Physiology-Endocrinology and Metabolism

123

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Ceramides and sphingolipids are a family of lipid molecules that circulate in serum and accumulate in skeletal muscle, promoting insulin resistance. Plasma ceramide and dihydroceramide are related to insulin resistance, yet less is known regarding other ceramide and sphingolipid species. Despite its association with insulin sensitivity, chronic endurance exercise training does not change plasma ceramide and sphingolipid content, with little known regarding a single bout of exercise. We measured basal relationships and the effect of acute exercise (1.5 h at 50% V O2 max) and recovery on serum ceramide and sphingolipid content in sedentary obese individuals, endurancetrained athletes, and individuals with type 2 diabetes (T2D). Basal serum C18:0, C20:0, and C24:1 ceramide and C18:0 and total dihydroceramide were significantly higher in T2D and, along with C16:0 ceramide and C18:0 sphingomyelin, correlated positively with insulin resistance. Acute exercise significantly increased serum ceramide, glucosylceramide, and GM3 gangliosides, which largely decreased to basal values in recovery. Sphingosine 1-phosphate and sphingomyelin did not change during exercise but decreased below basal values in recovery. Serum C16:0 and C18:0 ceramide and C18:0 sphingomyelin, but not the total concentrations of either of them, were positively correlated with markers of muscle NF-B activation, suggesting that specific species activate intracellular inflammation. Interestingly, a subset of sphingomyelin species, notably C14:0, C22:3, and C24:4 species, was positively associated with insulin secretion and glucose tolerance. Together, these data show that unique ceramide and sphingolipid species associate with either protective or deleterious features for diabetes and could provide novel therapeutic targets for the future. insulin sensitivity; athlete's paradox; lipid composition; plasma biomarkers THE GLOBAL BURDEN OF DIABETES continues to rise, fueled by the even greater epidemic of prediabetes (9). Nevertheless, not all of those with prediabetes will develop diabetes (27), highlighting the need to identify nonglycemic markers of disease progression that may also prove useful as new targets for the treatment of diabetes itself. Advances in lipidomics have provided new tools to investigate processes that govern the development of diabetes and its complications beyond that of glucose itself. Serum ceramides, a family of sphingolipids involved in diverse and relevant metabolic processes, have received considerable attention in relation to diabetes, making them prime candidates for further examination. Unlike other biomarkers, discrete serum ceramide profiles are rendered across the spectrum of diabetogenesis, creating speculation that ceramides not only mark but contribute to the disease process (8, 17).Much of this speculation is derived from data generated from in vitro and animal experimentation. Human data to date are limited largely to associations between serum ceramide concentration and risk for both diabetes (15) and related comp...

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“…Changes in the HOMA-IR also positively correlate with changes in the SM (d18:0/16:1). Hanamatsu et al [32] demonstrate that the high levels of serum SM species with distinct saturated acyl chains including C18:0 closely correlate with the HOMA-IR and BMI. These results suggest that BCAAs, aromatic amino acids, and SM, as observed in our study as L-leucine, L-phenylalanine, and SM (d18:0/16:1), are associated with the development of IR.…”

Section: Resultsmentioning

confidence: 99%

Global Metabolic Profiling of Plasma Shows that Three-Year Mild-Caloric Restriction Lessens an Age-Related Increase in Sphingomyelin and Reduces L-leucine and L-phenylalanine in Overweight and Obese Subjects

Kim

Lee²,

Lee

2016

Aging and disease

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The effect of weight loss from long-term, mild-calorie diets (MCD) on plasma metabolites is unknown. This study was to examine whether MCD-induced weight reduction caused changes in the extended plasma metabolites. Overweight and obese subjects aged 4059 years consumed a MCD (approximately 100 kcal/day deficit, n=47) or a weight-maintenance diet (control, n=47) in a randomized, controlled design with a three-year clinical intervention period and plasma samples were analyzed by using UPLC-LTQ-Orbitrap mass spectrometry. The three-year MCD intervention resulted in weight loss (-8.87%) and significant decreases in HOMA-IR and TG. The three-year follow-up of the MCD group showed reductions in the following 13 metabolites: L-leucine; L-phenylalanine; 9 lysoPCs; PC (18:0/20:4); and SM (d18:0/16:1). The three-year MCD group follow-up identified increases in palmitic amide, oleamide, and PC (18:2/18:2). Considering the age-related alterations in the identified metabolites, the MCD group showed a greater decrease in L-leucine, L-phenylalanine, and SM (d18:0/16:1) compared with those of the control group. Overall, the change (△) in BMI positively correlated with the △TG, △HOMA-IR, △L-leucine, and △SM (d18:0/16:1). The △HOMA-IR positively correlated with △TG, △L-leucine, △L-phenylalanine, and △SM (d18:0/16:1). The weight loss resulting from three-year mildcaloric restriction lessens the age-related increase in SM and reduces L-leucine and L-phenylalanine in overweight and obese subjects. These changes were coupled with improved insulin resistance (ClinicalTrials.gov: NCT02081898).

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Altered levels of serum sphingomyelin and ceramide containing distinct acyl chains in young obese adults

Cited by 140 publications

References 34 publications

Plasma cross-gestational sphingolipidomic analyses reveal potential first trimester biomarkers of preeclampsia

Plasma cross-gestational sphingolipidomic analyses reveal potential first trimester biomarkers of preeclampsia

Serum sphingolipids: relationships to insulin sensitivity and changes with exercise in humans

Global Metabolic Profiling of Plasma Shows that Three-Year Mild-Caloric Restriction Lessens an Age-Related Increase in Sphingomyelin and Reduces L-leucine and L-phenylalanine in Overweight and Obese Subjects

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