Sphingolipids in human ileostomy content after meals containing milk sphingomyelin

Ohlsson, Lena; Hertervig, Erik; Jönsson, Bo; Duan, Rui‐Dong; Nyberg, Lena; Svernlöv, Rikard; Nilsson, Åke

doi:10.3945/ajcn.2009.28311

Cited by 61 publications

(45 citation statements)

References 30 publications

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“…The regulation of proliferation rather than the induction of apoptosis was evident in all studies, which likely accounts for the lack of deleterious side effects noted using this route of administration. Throughout the intestinal tract, complex sphingolipids are hydrolyzed to the bioactive metabolites Cer and Sph, which are taken up by the intestinal cells; a small percentage of mostly free sphingoid bases reaches systemic distribution [24,25] in sufficient amounts to suppress experimental liver [26] and breast cancer [27] in rodents. Our recent studies have revealed a significant disruption of the actin cytoskeleton during malignant progression, suggesting a link between cytoskeleton dysregulation and neoplastic progression.…”

Section: Introductionmentioning

confidence: 99%

Regulation of Cytoskeleton Organization by Sphingosine in a Mouse Cell Model of Progressive Ovarian Cancer

et al. 2013

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Ovarian cancer is a multigenic disease and molecular events driving ovarian cancer progression are not well established. We have previously reported the dysregulation of the cytoskeleton during ovarian cancer progression in a syngeneic mouse cell model for progressive ovarian cancer. In the present studies, we investigated if the cytoskeleton organization is a potential target for chemopreventive treatment with the bioactive sphingolipid metabolite sphingosine. Long-term treatment with non-toxic concentrations of sphingosine but not other sphingolipid metabolites led to a partial reversal of a cytoskeleton architecture commonly associated with aggressive cancer phenotypes towards an organization reminiscent of non-malignant cell phenotypes. This was evident by increased F-actin polymerization and organization, a reduced focal adhesion kinase expression, increased α-actinin and vinculin levels which together led to the assembly of more mature focal adhesions. Downstream focal adhesion signaling, the suppression of myosin light chain kinase expression and hypophosphorylation of its targets were observed after treatment with sphingosine. These results suggest that sphingosine modulate the assembly of actin stress fibers via regulation of focal adhesions and myosin light chain kinase. The impact of these events on suppression of ovarian cancer by exogenous sphingosine and their potential as molecular markers for treatment efficacy warrants further investigation.

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Section: Introductionmentioning

confidence: 99%

Regulation of Cytoskeleton Organization by Sphingosine in a Mouse Cell Model of Progressive Ovarian Cancer

et al. 2013

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“…In contrast, in humans the hydrolysis of SM is faster and more efficient than rodents as SMase is secreted into the bile [23]. Recently it has been demonstrated that humans can digest and absorb most of the SM consumed in normal diets [24]. It has also been reported that enzymes responsible for digestion of SM including intestinal alkaline SMase and ceramidase are well expressed in humans [25,26].…”

Section: Discussionmentioning

confidence: 99%

Effect of dietary sphingomyelin on absorption and fractional synthetic rate of cholesterol and serum lipid profile in humans

et al. 2013

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BackgroundDiets enriched with sphingolipids may improve blood lipid profiles. Studies in animals have shown reductions in cholesterol absorption and alterations in blood lipids after treatment with sphingomyelin (SM). However, minimal information exists on effect of SM on cholesterol absorption and metabolism in humans. The objective was to assess the effect of SM consumption on serum lipid concentrations and cholesterol metabolism in healthy humans.MethodsTen healthy adult males and females completed a randomized crossover study. Subjects consumed controlled diets with or without 1 g/day SM for 14 days separated by at least 4 week washout period. Serum lipid profile and markers of cholesterol metabolism including cholesterol absorption and synthesis were analyzed.ResultsSerum triglycerides, total, LDL- and VLDL- cholesterol were not affected while HDL cholesterol concentrations were increased (p = 0.043) by SM diet consumption. No change in cholesterol absorption and cholesterol fractional synthesis rate was observed with supplementation of SM compared to control. Intraluminal cholesterol solubilization was also not affected by consumption of SM enriched diet.ConclusionsIn humans, 1 g/day of dietary SM does not alter the blood lipid profile except for an increased HDL-cholesterol concentration and has no effect on cholesterol absorption, synthesis and intraluminal solubilization compared to control.Trial registrationClinicaltrials.gov # NCT00328211

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“…Animal studies proved that consumed SM is digested only partially and it is a slow process [34]. On the other hand, in human more than 80% of SM can be digested, and the rest is excreted with feces [35]. SM is resistant to digestion by pancreatic enzymes [2].…”

Section: Physiological Role Of Sphingolipids In Gastrointestinal Tmentioning

confidence: 99%

Metabolism, Physiological Role, and Clinical Implications of Sphingolipids in Gastrointestinal Tract

Kurek

Łukaszuk

Piotrowska

et al. 2013

BioMed Research International

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Sphingolipids in digestive system are responsible for numerous important physiological and pathological processes. In the membrane of gut epithelial cells, sphingolipids provide structural integrity, regulate absorption of some nutrients, and act as receptors for many microbial antigens and their toxins. Moreover, bioactive sphingolipids such as ceramide or sphingosine-1-phosphate regulate cellular growth, differentiation, and programmed cell death—apoptosis. Although it is well established that sphingolipids have clinical implications in gastrointestinal tumorigenesis or inflammation, further studies are needed to fully explore the role of sphingolipids in neoplastic and inflammatory diseases in gastrointestinal tract. Pharmacological agents which regulate metabolism of sphingolipids can be potentially used in the management of colorectal cancer or inflammatory bowel diseases. The aim of this work is to critically the review physiological and pathological roles of sphingolipids in the gastrointestinal tract.

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Sphingolipids in human ileostomy content after meals containing milk sphingomyelin

Abstract: Humans digest and absorb most of the sphingomyelin in normal diets. The amount of sphingolipid metabolites to which the colon is exposed can, however, be influenced by realistic amounts of dietary sphingomyelin.

Cited by 61 publications

References 30 publications

Regulation of Cytoskeleton Organization by Sphingosine in a Mouse Cell Model of Progressive Ovarian Cancer

Regulation of Cytoskeleton Organization by Sphingosine in a Mouse Cell Model of Progressive Ovarian Cancer

Effect of dietary sphingomyelin on absorption and fractional synthetic rate of cholesterol and serum lipid profile in humans

Metabolism, Physiological Role, and Clinical Implications of Sphingolipids in Gastrointestinal Tract

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