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Background: A growing body of research indicates that associations of ceramides and sphingomyelins with mortality depend on the chain length of the fatty acid acylated to the backbone sphingoid base. We examined associations of 8 ceramide and sphingomyelin species with mortality among an American Indian population., Methods and Results: The analysis comprised 2688 participants from the SHFS (Strong Heart Family Study). Plasma ceramide and sphingomyelin species carrying long-chain (ie, 16:0) and very-long-chain (ie, 20:0, 22:0, 24:0) saturated fatty acids were measured by sequential liquid chromatography and mass spectroscopy using samples from 2001 to 2003. Participants were followed for 18.8 years (2001-2020). Associations of ceramides and sphingomyelins with mortality were assessed using Cox models. The mean age of participants was 40.8 years. There were 574 deaths during a median 17.4-year follow-up. Ceramides and sphingomyelins carrying fatty acid 16:0 were positively associated with mortality. Ceramides and sphingomyelins carrying longer fatty acids were inversely associated with mortality. Per SD difference in each ceramide and sphingomyelin species, hazard ratios for death were: 1.68 (95% CI, 1.44-1.96) for ceramide-16 (Cer-16), 0.82 (95% CI, 0.71-0.95) for Cer-20, 0.60 (95% CI, 0.51-0.70) for Cer-22, 0.67 (95% CI, 0.56-0.79) for Cer-24, 1.80 (95% CI-1.57, 2.05) for sphingomyelin-16 (SM-16), 0.54 (95% CI, 0.47-0.62) for SM-20, 0.50 (95% CI, 0.44-0.57) for SM-22, and 0.59 (95% CI, 0.52-0.67) for SM-24., Conclusions: The direction/magnitude of associations of ceramides and sphingomyelins with mortality differs according to the length of the fatty acid acylated to the backbone sphingoid base., Registration: URL: https://www.clinicatrials.gov; Unique identifier: NCT00005134.

Introduction In a randomised controlled study, the use of ceramide-infused skin barriers (CIB) resulted in lower costs of care over 12 weeks versus using a standard of care (SoC) skin barrier. However, the degree to which this information may influence prescribing patterns of ostomy products, and its corresponding impact on payers' budgets, has not been examined. Purpose To examine expected budget impact of CIB among recent ostomates in the United States (US), the United Kingdom (UK), Sweden, Australia, Italy and Norway. Design A decision-analytic budget impact model. Methods Total ostomy-related costs (i.e., skin barriers, ostomy accessories, care of peristomal skin complications [PSC]) were forecasted over 1 year for hypothetical cohorts of recent ostomates in each country of interest. Costs were assessed under two alternative scenarios -- one in which all patients were assumed to use barriers other than CIB (the SoC scenario), and one in which 20% of patients were assumed to use CIB in lieu of SoC (the CIB scenario). The budget impact was assumed equal to the difference in these two scenarios. Findings The use of CIB was expected to result in annual savings of US$6.6m in the US, £0.4m in the UK, SEK1.8m in Sweden, A$0.4m in Australia, €0.2m in Italy and NOK1.5m in Norway. Findings were consistent in sensitivity analyses. Conclusions The use of CIB versus other barriers results in expected lower costs to the payers in each evaluated country. Further research is needed to better understand the complete clinical and economic benefits associated with the use of CIB. [ABSTRACT FROM AUTHOR]

Background: Obesity is a prevalent health threat and risk factor for type 2 diabetes. In this study, we evaluate the relationship between ceramides, which inhibit insulin secretion and sensitivity, and markers of glucose homeostasis and diabetes remission or recursion in patients who have undergone a Roux-en-Y gastric bypass (RYGB)., Methods: The Utah Obesity Study is a prospective cohort study, with targeted ceramide and dihydroceramide measurements performed on banked serum samples. The Utah Obesity Study consists of 1,156 participants in three groups: a RYGB surgery group, a non-surgery group denied insurance coverage, and severely obese population controls. Clinical examinations and ceramide assessments were performed at baseline and 2 and 12 years after RYGB surgery., Findings: Surgery patients (84% female, 42.2 ± 10.6 years of age at baseline) displayed lower levels of several serum dihydroceramides and ceramides at 2 and 12 years after RYGB. By contrast, neither the control group (77% female, 48.7± 6.4 years of age at baseline) nor the non-surgery group (95% female, 43.0± 11.4 years of age at baseline) experienced significant decreases in any species. Using a linear mixed effect model, we found that multiple dihydroceramides and ceramides positively associated with the glycemic control measures HOMA-IR and HbA1c. In surgery group participants with prevalent diabetes, ceramides inversely predict diabetes remission, independent of changes in weight., Conclusions: Ceramide decreases may explain the insulin sensitization and diabetes resolution observed in most RYGB surgery patients., Funding: Funded by the National Institutes of health (NIH), The Juvenile Diabetes Research Foundation, and the American Heart Association., Competing Interests: Declaration of interests S.A.S. is a cofounder of, consultant to, and shareholder in Centaurus Therapeutics. A.M.P., B.K., J.A.M., B.H., J.E.C., Y.L., T.S.T., P.K., A.I., S.C.H., T.D.A., M.C.P., and W.L.H. have no conflicts of interest to declare., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Atopic dermatitis is the most common chronic inflammatory skin condition seen in the pediatric population. In the United States, the prevalence rate of atopic dermatitis is 10 to 12 percent in children. A nonsteroidal, barrier repair product consisting of an optimal ratio of ceramides, cholesterol, and free-fatty acids has been demonstrated to be efficacious and safe in the treatment of atopic dermatitis in previous clinical trials. This report is a subgroup analysis of the efficacy and safety of this nonsteroidal, ceramide-dominant, physiological lipid-based topical emulsion used among 59 patients, three months to 16 years of age, with mild-to-moderate atopic dermatitis. Treatment success based on an Investigator Global Assessment rating of clear or almost clear was achieved by 58 percent of subjects after use of the ceramide-dominant, physiological lipid barrier repair emulsion for three weeks as monotherapy or in combination with another topical atopic dermatitis treatment. The severity of pruritus decreased markedly from Baseline to Week 3 overall regardless of disease severity at baseline. A large percentage of subjects (71%) reported satisfaction with clinical results. After three weeks of treatment, a significant number of subjects reported less worry about their atopic dermatitis compared to baseline. The results further support other publications that suggest a treatment approach that incorporates an optimized formulation of a skin barrier repair cream as an integral component of initial atopic dermatitis therapy, either as monotherapy or as part of combination topical therapy. [ABSTRACT FROM AUTHOR]

Aim: Adenocarcinoma of the prostate is one of the most frequently diagnosed non-cutaneous cancers and the second leading cause of cancer-related deaths among men in the United States. To fully understand the role of ceramide during apoptosis induced by androgen ablation, we modified the levels of intracellular ceramide by pharmacological agents as well as through serum deprivation in androgen-dependent and independent cell lines. Methods: Ceramide levels were modified using N-oleoylethanolamine (NOE), sphingosine-1-phosphate (S1P) as well as through serum deprivation, in LNCaP, DU145 and PC-3 prostate cancer cells. Various methods including nonyl acridine orange staining, propidium iodide staining/cell cycle analysis and lipid analysis were utilized. Results: Our results demonstrate that the inhibition of acid ceramidase by NOE enhances the intracellular ceramide levels induced by androgen ablation in androgen-dependent LNCaP cells, and is accompanied by an increase in apoptotic cells. Sphingosine 1-phosphate had no effect in rescuing LNCaP cells from apoptosis induced by androgen ablation. Our results also show that serum deprivation causes intracellular ceramide accumulation and apoptosis in androgen-independent prostate cancer cells. Conclusions: Our studies indicate that the increase in intracellular ceramide itself, but not the balance between ceramide and S1P, determines whether LNCaP cells undergo apoptosis. Our results also show that the increase in intracellular ceramide strongly correlates with apoptosis induced by serum deprivation even in androgen-independent prostate cancer cell lines. [ABSTRACT FROM AUTHOR]

Background/purpose: Sphingolipids are major constituents of eukaryotic cell membranes and play key roles in cellular regulatory processes. Our recent results in an experimental stroke animal model demonstrated changes in sphingolipids in response to acute ischemic brain injury. This study aimed to investigate the plasma levels of sphingosine-1-phosphate (S1P) and ceramides in acute ischemic stroke (AIS) patients and their associations with functional outcomes., Methods: Plasma samples were collected from patients with AIS at <48 and 48-72 h post stroke and from nonstroke controls. The levels of S1P and ceramides with different fatty acyl chain lengths were measured by the ultra-high-pressure liquid chromatography-electrospray ionization tandem mass spectrometry (UHPLC-ESI-MS/MS). A poor functional outcome was defined as a modified Rankin Scale (mRS) score ≥2 at 3 months after AIS., Results: The results showed that S1P and very-long-chain ceramides were significantly decreased in AIS patients (n = 87; poor outcome, 56.3%) compared to nonstroke controls (n = 30). In contrast, long-chain ceramides were significantly increased in AIS patients. More importantly, higher levels of Cer(d18:1/18:0), Cer(d18:1/20:0), and Cer(d18:1/22:0) at 48-72 h were significantly associated with poor functional outcomes after adjusting for potential clinical confounders, including age, sex, hypertension, and National Institutes of Health Stroke Scale score at admission., Conclusion: Our study supported the dynamic metabolism of sphingolipids after the occurrence of AIS. Ceramides could be potential prognostic markers for patients with AIS., Competing Interests: Declaration of competing interest The authors have no conflicts of interest relevant to this article., (Copyright © 2021. Published by Elsevier B.V.)

Metabolic syndrome (MetS) affects an increasing number of older adults worldwide. Cross-cultural comparisons can provide insight into how factors, including genetic, environmental, and lifestyle, may influence MetS prevalence. Metabolomics, which measures the biochemical products of cell processes, can be used to enhance a mechanistic understanding of how biological factors influence metabolic outcomes. In this study we examined associations between serum metabolite concentrations, representing a range of biochemical pathways and metabolic syndrome in two older adult cohorts: The Tsuruoka Metabolomics Cohort Study (TMCS) from Japan ( n = 104) and the Baltimore Longitudinal Study of Aging (BLSA) from the United States ( n = 146). We used logistic regression to model associations between MetS and metabolite concentrations. We found that metabolites from the phosphatidylcholines-acyl-alkyl, sphingomyelin, and hexose classes were significantly associated with MetS and risk factor outcomes in both cohorts. In BLSA, metabolites across all classes were uniquely associated with all outcomes. In TMCS, metabolites from the amino acid, biogenic amines, and free fatty acid classes were uniquely associated with MetS, and metabolites from the sphingomyelin class were uniquely associated with elevated triglycerides. The metabolites and metabolite classes we identified may be relevant for future studies exploring disease mechanisms and identifying novel precision therapy targets for individualized medicine.

Background: Obesity is considered problematic not only as a major cause of diabetes, hypertension, and dyslipidemia, but also as a risk of intractable dermatosis; however influence of obesity on skin function has not been clarified. To clarify the mechanism of obesity-associated skin disorders, we aimed to characterize the skin function of subjects with obesity, and identify possible influencing factors., Methods: Complex analyses including instrumental measurement, biochemical and lipidomics were performed for facial skin and physical evaluation in 93 Caucasian women with obesity (OB) and non-obesity (NOB)., Results: In OB, imbalance in metabolism of carbohydrate and lipid, autonomic nerve activity, and secreted factors were confirmed. In the skin properties in OB, surface roughness was higher by 70%, the water content was lower by 12%, and changes in the lipid profile of stratum corneum ceramide were observed; in particular, a 7% reduction of [NP]-type ceramide, compared with NOB. Moreover, significant redness accompanied by a 34% increase in skin blood flow was observed in OB. Correlation analysis elucidated that the water content was strongly correlated with local skin indices, such as the ceramide composition, redness, blood flow, and TNFα in the stratum corneum, whereas roughness was correlated with the systemic indices, such as serum insulin, leptin, and IL-6., Conclusions: Characteristics of obesity-associated skin were (A) reduction of the barrier and moisturizing function accompanied by intercellular lipid imbalance, (B) increased redness accompanied by hemodynamic changes, and (C) surface roughness. It was suggested that each symptom is due to different causes in local and/or systemic physiological impairment related to the autonomic nerve-vascular system, inflammation and insulin resistance.